CN108490188A - Breast cancer risk assessment protein and its application - Google Patents

Breast cancer risk assessment protein and its application Download PDF

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CN108490188A
CN108490188A CN201810186862.6A CN201810186862A CN108490188A CN 108490188 A CN108490188 A CN 108490188A CN 201810186862 A CN201810186862 A CN 201810186862A CN 108490188 A CN108490188 A CN 108490188A
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value
breast cancer
fip200
status
risk
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王鹏
裴雨晨
薛梦竹
刘雨薇
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Shanghai Advanced Research Institute of CAS
University of Chinese Academy of Sciences
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University of Chinese Academy of Sciences
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57484Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6893Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00Detection or diagnosis of diseases
    • G01N2800/36Gynecology or obstetrics
    • G01N2800/365Breast disorders, e.g. mastalgia, mastitits, Paget's disease
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00Detection or diagnosis of diseases
    • G01N2800/70Mechanisms involved in disease identification
    • G01N2800/7023(Hyper)proliferation
    • G01N2800/7028Cancer

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Abstract

The invention belongs to therapeutic field of tumor, and in particular to a kind of breast cancer risk assessment protein and its application.Inventor has found, by detecting the expression of ATG5 and FIP200 in sample, to can recognize that the sample of ATG5 and FIP200 low expressions, and can further predict such sample for the poor type of high risk, prognosis.In addition, expression data and survival data through 200 breast cancer patients samples confirm, pass through the characterization of ATG5 and FIP200 expression quantity, the sample of high risk, poor prognosis can effectively be predicted, it is seen that ATG5 and FIP200 has high industrial utilization on the way in the use of the drug or kit of preparation or Screening Diagnosis breast cancer or the drug of screening treatment breast cancer.

Description

Breast cancer risk assessment protein and its application
Technical field
The invention belongs to therapeutic field of tumor, and in particular to a kind of breast cancer risk assessment protein and its application.
Background technology
Cancer is to endanger one of chief complaint of human health at present, annual China only because of the number of tumor mortality just nearly 2000000 people.And breast cancer is one of the most common malignant tumors in women in global range, and cause the important original of women die Cause.In China, as other most countries, breast cancer also becomes the most common cancer of Chinese women;Annual China's breast Gland cancer newly sends out 12.2% and 9.6% that quantity and The dead quantity account for world population respectively, annual new cases about 210,000, China's breast Gland cancer incidence growth rate, is higher by 1-2 percentage points of developed country.With the application of new technology novel drugs etc., early stage mammary gland The cure rate of cancer can reach 90%, however still have the patient of 30%-40% that can die of breast cancer relapse.
After the onset of prognosis refers to, one kind of disease future course is pre-estimated.Medically, " prognosis " refers to rule of thumb The disease development of prediction.Prognosis is mainly concerned with three aspects, the possibility that result will occur, bad result occurs Have it is much, when occur.Prognostic analysis is the prediction to developing into various different outcomes after disease incidence;Be it is clinical very Clinical research that is practical, having very much directive function to clinic.The purpose of research and grading prognosis, for the ease of understanding various diseases pair The size of mankind's harmfulness explores the factor for influencing prognosis, the concrete measure of research improvement prognosis.
Tumour marker is can be detected in serum, blood plasma, other body fluid, tissue extract or the fixed tissue of paraffin The naturally produced molecule arrived.Tumour marker can be the diagnosis of breast cancer, the selection of therapeutic scheme, disease process and recurrence Prediction and the monitoring etc. of therapeutic effect valuable information is provided.Breast cancer lacks very much as women malignant tumour occurred frequently Efficient tumour marker.The breast cancer marker that China clinically applies at present have estrogen receptor (ER), progestational hormone by Body (PR) and HER2 genes, common breast cancer classification are also to be classified according to these three markers.But in same hypotype, no With the prognosis of patient, time-to-live, whether recurs etc. and all there is significant difference.How accurate parting to be carried out to breast cancer, is use up It is early judge tumour whether can Preventive select rational treatment means in turn, improve survival rate and the existence of patient with breast cancer Quality is the important developing direction of breast cancer treatment.
Invention content
In order to overcome the defects of the prior art, the purpose of the present invention is to provide ATG5 albumen combines with FIP200 albumen It is used to prepare or screens the purposes of Prognosis in Breast Cancer assessment reagent.
It should be noted that in the present invention, ATG5 albumen is referred to as ATG5, full name in English autophagy- related gene 5.In the present invention, FIP200 albumen is referred to as FIP200, and FIP200 is FAK protein families (FAK Family kinase-interacting protein) molecular weight be 200kDa kinase protein.
Another object of the present invention is to provide the reagents of specific recognition ATG5 albumen and FIP200 albumen to prepare mammary gland Purposes in cancer prognosis evaluation reagent kit.
Another object of the present invention is to provide a kind of Prognosis in Breast Cancer to assess kit.
Another object of the present invention is to provide ATG5 albumen to combine with FIP200 albumen as Prognosis in Breast Cancer assessment mark The purposes of will object.
Another object of the present invention is to provide a kind of Prognosis in Breast Cancer appraisal procedures.
Another object of the present invention is to provide a kind of Prognosis in Breast Cancer apparatus for evaluating.
It is stored with based on the computer program that Prognosis in Breast Cancer is assessed another object of the present invention is to provide a kind of Calculation machine readable storage medium storing program for executing.
The present invention is achieved by the following technical solutions:
The first aspect of the present invention, provides ATG5 albumen and combines with FIP200 albumen and be used to prepare or screen Prognosis in Breast Cancer Assess the purposes of reagent.
Wherein, ATG5 albumen is combined with FIP200 albumen is used to prepare Prognosis in Breast Cancer assessment reagent, refers to by ATG5 eggs Combine in vain with FIP200 albumen and is applied to the preparation that Prognosis in Breast Cancer assesses reagent as Prognosis in Breast Cancer evaluation index.For example, It can be directly using ATG5 albumen and FIP200 albumen as standard items or positive control, for ATG5 albumen in breast cancer tissue's sample With the detection of FIP200 protein levels.
Wherein, ATG5 albumen is combined with FIP200 albumen assesses reagent for screening Prognosis in Breast Cancer, refers to by ATG5 eggs Combine in vain with FIP200 albumen and is applied to the screening that Prognosis in Breast Cancer assesses reagent as Prognosis in Breast Cancer evaluation index.For example, Candidate substances can be screened, using the reagent and specific recognition of the specific recognition ATG5 albumen that screening obtains The reagent of FIP200 albumen detects ATG5 albumen and FIP200 protein levels in breast cancer tissue's sample.
The reagent of specific recognition ATG5 albumen can be the antibody or ligand of specific recognition ATG5 albumen.The antibody Including including monoclonal antibody and polyclonal antibody.As cited in the embodiment of the present invention, specific recognition ATG5 albumen Reagent can be the anti-ATG5 polyclonal antibodies 10181-2-AP (Proteintech Group, Chicago, IL, USA) of rabbit.
The reagent of specific recognition FIP200 albumen can be the antibody or ligand of specific recognition FIP200 albumen.It is described Antibody includes monoclonal antibody and polyclonal antibody.As cited in the embodiment of the present invention, specific recognition FIP200 Protein reagent can be rabbit anti-FIP200 polyclonal antibodies 16172-1-AP (Proteintech Group, Chicago, IL, USA)。
The second aspect of the present invention, provides specific recognition ATG5 albumen and the reagent of FIP200 albumen is preparing breast cancer Purposes in prognosis evaluation reagent kit.
The reagent of specific recognition ATG5 albumen can be the antibody or ligand of specific recognition ATG5 albumen.The antibody Including including monoclonal antibody and polyclonal antibody.As cited in the embodiment of the present invention, specific recognition ATG5 albumen Reagent can be the anti-ATG5 polyclonal antibodies 10181-2-AP (Proteintech Group, Chicago, IL, USA) of rabbit.
The reagent of specific recognition FIP200 albumen can be the antibody or ligand of specific recognition FIP200 albumen.It is described Antibody includes monoclonal antibody and polyclonal antibody.As cited in the embodiment of the present invention, specific recognition FIP200 Protein reagent can be rabbit anti-FIP200 polyclonal antibodies 16172-1-AP (Proteintech Group, Chicago, IL, USA)。
In the third aspect of the present invention, a kind of Prognosis in Breast Cancer assessment kit is provided, in the kit at least Reagent containing specific recognition ATG5 albumen Yu FIP200 albumen.
The reagent of specific recognition ATG5 albumen can be the antibody or ligand of specific recognition ATG5 albumen.The antibody Including including monoclonal antibody and polyclonal antibody.As cited in the embodiment of the present invention, specific recognition ATG5 albumen Reagent can be the anti-ATG5 polyclonal antibodies 10181-2-AP (Proteintech Group, Chicago, IL, USA) of rabbit.
The reagent of specific recognition FIP200 albumen can be the antibody or ligand of specific recognition FIP200 albumen.It is described Antibody includes monoclonal antibody and polyclonal antibody.As cited in the embodiment of the present invention, specific recognition FIP200 Protein reagent can be rabbit anti-FIP200 polyclonal antibodies 16172-1-AP (Proteintech Group, Chicago, IL, USA)。
In the fourth aspect of the present invention, provides ATG5 albumen and combine with FIP200 albumen as Prognosis in Breast Cancer assessment mark The purposes of will object.
The fifth aspect of the present invention provides a kind of Prognosis in Breast Cancer appraisal procedure, includes the following steps:
(1) Prognosis in Breast Cancer value-at-risk M is calculatedcombined, the Mcombined=-0.69x SAge+0.62x SMenopausal Status–1.24x S PR status+0.85x SLymph node status-0.74x SIATG5–0.74x SFIP200
(2) according to value-at-risk McombinedAssess Prognosis in Breast Cancer risk.
Further, SAgeIt refer to the variate-value divided according to the age of patient.
In a kind of embodiment, if the age of patient is more than 50 years old, SAgeValue is 2, if the age of patient is less than Or it is equal to 50 years old, then SAgeValue is 1.
Further, SMenopausal StatusBe according to patient whether menopause divide variate-value.
In a kind of embodiment, if patient's menopause, SMenopausal StatusValue is 2, if the non-menopause of patient, Then SMenopausal StatusValue is 1.
Further, SPR statusIt is the variate-value divided according to the progesterone receptor status of patient.
In a kind of embodiment, if the progesterone receptor status of patient is the positive, SPR statusValue is 2, if The progesterone receptor status of patient is feminine gender, then SPR statusValue is 1.The yin and yang attribute of progesterone receptor status divides, and belongs to The prior art is divided according to method in the prior art.
Further, SLymph node statusIt is to be drawn according to whether the breast cancer cell of patient is transferred into lymph node The variate-value divided.
In a kind of embodiment, if the breast cancer cell of patient is transferred into lymph node, SLymph node statusIt takes Value is 2, if the breast cancer cell of patient is not diverted into lymph node, SLymph node statusValue is 1.
Further, SIATG5Refer to the SI (staining according to the immunohistochemical staining of the breast cancer tissue of patient Index the variate-value) divided.The numberical range of SI is 0~9.
Specifically, in a kind of embodiment, score value proportional SI=staining power score values x, those skilled in the art can Rule of thumb range estimation judges staining power being divided into four different grades, when staining power is negative, staining power score value It is 0, when staining power is weak, staining power score value is 1;When staining power is middle, staining power score value is 2;Work as dyeing When intensity is strong, staining power score value is 3, and proportional score value is divided by the cell accounting being colored, when what is be colored When cell accounting is 0-10%, proportional score value is 1, when the cell accounting being colored is 10%-50%, proportional point Value is 2, and when the cell accounting being colored is 50% or more, proportional score value is 3.
Further, SFIP200It is positive according to the FIP200 of the breast cancer tissue of patient expression to refer to or feminine gender divides Variate-value.
In a kind of embodiment, as long as there is FIP200 expression in nucleus, then regard as being that FIP200 expression is positive, instead To be identified as FIP200 expression negative, when FIP200 is expressed it is positive when, SFIP200Value be 2, when FIP200 express it is negative When, SFIP200Value be 1.
Further, value-at-risk McombinedMore than threshold value, then it is evaluated as high risk, if value-at-risk McombinedIt is less than or equal to Threshold value is then evaluated as low-risk.
In a kind of embodiment, if value-at-risk McombinedMore than -0.397, then it is evaluated as high risk, if value-at-risk McombinedLess than or equal to -0.397, then low-risk is evaluated as.
The sixth aspect of the present invention provides a kind of Prognosis in Breast Cancer apparatus for evaluating, including:
Prognosis in Breast Cancer value-at-risk McombinedComputing module, for calculating Prognosis in Breast Cancer value-at-risk Mcombined, described Mcombined=-0.69x SAge+0.62x SMenopausal Status–1.24x S PR status+0.85x SLymph node status- 0.74x SIATG5–0.74x SFIP200
Prognosis in Breast Cancer risk evaluation module, for according to value-at-risk McombinedAssess Prognosis in Breast Cancer risk.
Further, SAgeIt refer to the variate-value divided according to the age of patient.
In a kind of embodiment, if the age of patient is more than 50 years old, SAgeValue is 2, if the age of patient is less than Or it is equal to 50 years old, then SAgeValue is 1.
Further, SMenopausal StatusBe according to patient whether menopause divide variate-value.
In a kind of embodiment, if patient's menopause, SMenopausal StatusValue is 2, if the non-menopause of patient, Then SMenopausal StatusValue is 1.
Further, SPR statusIt is the variate-value divided according to the progesterone receptor status of patient.
In a kind of embodiment, if the progesterone receptor status of patient is the positive, SPR statusValue is 2, if The progesterone receptor status of patient is feminine gender, then SPR statusValue is 1.The yin and yang attribute of progesterone receptor status divides, and belongs to The prior art is divided according to method in the prior art.
Further, SLymph node statusIt is to be drawn according to whether the breast cancer cell of patient is transferred into lymph node The variate-value divided.
In a kind of embodiment, if the breast cancer cell of patient is transferred into lymph node, SLymph node statusIt takes Value is 2, if the breast cancer cell of patient is not diverted into lymph node, SLymph node statusValue is 1.
Further, SIATG5Refer to the SI (staining according to the immunohistochemical staining of the breast cancer tissue of patient Index the variate-value) divided.The numberical range of SI is 0~9.
Specifically, in a kind of embodiment, score value proportional SI=staining power score values x, those skilled in the art can Rule of thumb range estimation judges staining power being divided into four different grades, when staining power is negative, staining power score value It is 0, when staining power is weak, staining power score value is 1;When staining power is middle, staining power score value is 2;Work as dyeing When intensity is strong, staining power score value is 3, and proportional score value is divided by the cell accounting being colored, when what is be colored When cell accounting is 0-10%, proportional score value is 1, when the cell accounting being colored is 10%-50%, proportional point Value is 2, and when the cell accounting being colored is 50% or more, proportional score value is 3.
Further, SFIP200It is positive according to the FIP200 of the breast cancer tissue of patient expression to refer to or feminine gender divides Variate-value.
In a kind of embodiment, as long as there is FIP200 expression in nucleus, then regard as being that FIP200 expression is positive, instead To be identified as FIP200 expression negative, when FIP200 is expressed it is positive when, SFIP200Value be 2, when FIP200 express it is negative When, SFIP200Value be 1.
Further, if value-at-risk McombinedMore than threshold value, then it is evaluated as high risk, if value-at-risk McombinedLess than etc. In threshold value, then low-risk is evaluated as.
In a kind of embodiment, if value-at-risk McombinedMore than -0.397, then it is evaluated as high risk, if value-at-risk McombinedLess than or equal to -0.397, then low-risk is evaluated as.
The seventh aspect of the present invention provides a kind of Prognosis in Breast Cancer apparatus for evaluating, and described device includes computer, the meter Calculation machine is programmed to execute following steps:
(1) Prognosis in Breast Cancer value-at-risk M is calculatedcombined, the Mcombined=-0.69x SAge+0.62x SMenopausal Status–1.24x S PR status+0.85x SLymph node status-0.74x SIATG5–0.74x SFIP200
(2) according to value-at-risk McombinedAssess Prognosis in Breast Cancer risk.
Further, SAgeIt refer to the variate-value divided according to the age of patient.
In a kind of embodiment, if the age of patient is more than 50 years old, SAgeValue is 2, if the age of patient is less than Or it is equal to 50 years old, then SAgeValue is 1.
Further, SMenopausal StatusBe according to patient whether menopause divide variate-value.
In a kind of embodiment, if patient's menopause, SMenopausal StatusValue is 2, if the non-menopause of patient, Then SMenopausal StatusValue is 1.
Further, SPR statusIt is the variate-value divided according to the progesterone receptor status of patient.
In a kind of embodiment, if the progesterone receptor status of patient is the positive, SPR statusValue is 2, if The progesterone receptor status of patient is feminine gender, then SPR statusValue is 1.The yin and yang attribute of progesterone receptor status divides, and belongs to The prior art is divided according to method in the prior art.
Further, SLymph node statusIt is to be drawn according to whether the breast cancer cell of patient is transferred into lymph node The variate-value divided.
In a kind of embodiment, if the breast cancer cell of patient is transferred into lymph node, SLymph node statusIt takes Value is 2, if the breast cancer cell of patient is not diverted into lymph node, SLymph node statusValue is 1.
Further, SIATG5Refer to the SI (staining according to the immunohistochemical staining of the breast cancer tissue of patient Index the variate-value) divided.The numberical range of SI is 0~9.
Specifically, in a kind of embodiment, score value proportional SI=staining power score values x, those skilled in the art can Rule of thumb range estimation judges staining power being divided into four different grades, when staining power is negative, staining power score value It is 0, when staining power is weak, staining power score value is 1;When staining power is middle, staining power score value is 2;Work as dyeing When intensity is strong, staining power score value is 3, and proportional score value is divided by the cell accounting being colored, when what is be colored When cell accounting is 0-10%, proportional score value is 1, when the cell accounting being colored is 10%-50%, proportional point Value is 2, and when the cell accounting being colored is 50% or more, proportional score value is 3.
Further, SFIP200It is positive according to the FIP200 of the breast cancer tissue of patient expression to refer to or feminine gender divides Variate-value.
In a kind of embodiment, as long as there is FIP200 expression in nucleus, then regard as being that FIP200 expression is positive, instead To be identified as FIP200 expression negative, when FIP200 is expressed it is positive when, SFIP200Value be 2, when FIP200 express it is negative When, SFIP200Value be 1.
Further, if value-at-risk McombinedMore than threshold value, then it is evaluated as high risk, if value-at-risk McombinedLess than etc. In threshold value, then low-risk is evaluated as.
In a kind of embodiment, if value-at-risk McombinedMore than -0.397, then it is evaluated as high risk, if value-at-risk McombinedLess than or equal to -0.397, then low-risk is evaluated as.
The sixth aspect of the present invention provides a kind of Prognosis in Breast Cancer apparatus for evaluating, including:
Prognosis in Breast Cancer value-at-risk McombinedComputing module, for calculating Prognosis in Breast Cancer value-at-risk Mcombined, described Mcombined=-0.69x SAge+0.62x SMenopausal Status–1.24x S PR status+0.85x SLymph node status- 0.74x SIATG5–0.74x SFIP200
Prognosis in Breast Cancer risk evaluation module, for according to value-at-risk McombinedAssess Prognosis in Breast Cancer risk.
Further, SAgeIt refer to the variate-value divided according to the age of patient.
In a kind of embodiment, if the age of patient is more than 50 years old, SAgeValue is 2, if the age of patient is less than Or it is equal to 50 years old, then SAgeValue is 1.
Further, SMenopausal StatusBe according to patient whether menopause divide variate-value.
In a kind of embodiment, if patient's menopause, SMenopausal StatusValue is 2, if the non-menopause of patient, Then SMenopausal StatusValue is 1.
Further, SPR statusIt is the variate-value divided according to the progesterone receptor status of patient.
In a kind of embodiment, if the progesterone receptor status of patient is the positive, SPR statusValue is 2, if The progesterone receptor status of patient is feminine gender, then SPR statusValue is 1.The yin and yang attribute of progesterone receptor status divides, and belongs to The prior art is divided according to method in the prior art.
Further, SLymph node statusIt is to be drawn according to whether the breast cancer cell of patient is transferred into lymph node The variate-value divided.
In a kind of embodiment, if the breast cancer cell of patient is transferred into lymph node, SLymph node statusIt takes Value is 2, if the breast cancer cell of patient is not diverted into lymph node, SLymph node statusValue is 1.
Further, SIATG5Refer to the SI (staining according to the immunohistochemical staining of the breast cancer tissue of patient Index the variate-value) divided.The numberical range of SI is 0~9.
Specifically, in a kind of embodiment, score value proportional SI=staining power score values x, those skilled in the art can Rule of thumb range estimation judges staining power being divided into four different grades, when staining power is negative, staining power score value It is 0, when staining power is weak, staining power score value is 1;When staining power is middle, staining power score value is 2;Work as dyeing When intensity is strong, staining power score value is 3, and proportional score value is divided by the cell accounting being colored, when what is be colored When cell accounting is 0-10%, proportional score value is 1, when the cell accounting being colored is 10%-50%, proportional point Value is 2, and when the cell accounting being colored is 50% or more, proportional score value is 3.
Further, SFIP200It is positive according to the FIP200 of the breast cancer tissue of patient expression to refer to or feminine gender divides Variate-value.
In a kind of embodiment, as long as there is FIP200 expression in nucleus, then regard as being that FIP200 expression is positive, instead To be identified as FIP200 expression negative, when FIP200 is expressed it is positive when, SFIP200Value be 2, when FIP200 express it is negative When, SFIP200Value be 1.
Further, if value-at-risk McombinedMore than threshold value, then it is evaluated as high risk, if value-at-risk McombinedLess than etc. In threshold value, then low-risk is evaluated as.
In a kind of embodiment, if value-at-risk McombinedMore than -0.397, then it is evaluated as high risk, if value-at-risk McombinedLess than or equal to -0.397, then low-risk is evaluated as.
The eighth aspect of the present invention provides a kind of computer readable storage medium being stored with computer program, the meter Calculation machine program makes computer execute following steps:
(1) Prognosis in Breast Cancer value-at-risk M is calculatedcombined, the Mcombined=-0.69x SAge+0.62x SMenopausal Status–1.24x S PR status+0.85x SLymph node status-0.74x SIATG5–0.74x SFIP200
(2) according to value-at-risk McombinedAssess Prognosis in Breast Cancer risk.
Further, SAgeIt refer to the variate-value divided according to the age of patient.
In a kind of embodiment, if the age of patient is more than 50 years old, SAgeValue is 2, if the age of patient is less than Or it is equal to 50 years old, then SAgeValue is 1.
Further, SMenopausal StatusBe according to patient whether menopause divide variate-value.
In a kind of embodiment, if patient's menopause, SMenopausal StatusValue is 2, if the non-menopause of patient, Then SMenopausal StatusValue is 1.
Further, SPR statusIt is the variate-value divided according to the progesterone receptor status of patient.
In a kind of embodiment, if the progesterone receptor status of patient is the positive, SPR statusValue is 2, if The progesterone receptor status of patient is feminine gender, then SPR statusValue is 1.The yin and yang attribute of progesterone receptor status divides, and belongs to The prior art is divided according to method in the prior art.
Further, SLymph node statusIt is to be drawn according to whether the breast cancer cell of patient is transferred into lymph node The variate-value divided.
In a kind of embodiment, if the breast cancer cell of patient is transferred into lymph node, SLymph node statusIt takes Value is 2, if the breast cancer cell of patient is not diverted into lymph node, SLymph node statusValue is 1.
Further, SIATG5Refer to the SI (staining according to the immunohistochemical staining of the breast cancer tissue of patient Index the variate-value) divided.The numberical range of SI is 0~9.
Specifically, in a kind of embodiment, score value proportional SI=staining power score values x, those skilled in the art can Rule of thumb range estimation judges staining power being divided into four different grades, when staining power is negative, staining power score value It is 0, when staining power is weak, staining power score value is 1;When staining power is middle, staining power score value is 2;Work as dyeing When intensity is strong, staining power score value is 3, and proportional score value is divided by the cell accounting being colored, when what is be colored When cell accounting is 0-10%, proportional score value is 1, when the cell accounting being colored is 10%-50%, proportional point Value is 2, and when the cell accounting being colored is 50% or more, proportional score value is 3.
Further, SFIP200It is positive according to the FIP200 of the breast cancer tissue of patient expression to refer to or feminine gender divides Variate-value.
In a kind of embodiment, as long as there is FIP200 expression in nucleus, then regard as being that FIP200 expression is positive, instead To be identified as FIP200 expression negative, when FIP200 is expressed it is positive when, SFIP200Value be 2, when FIP200 express it is negative When, SFIP200Value be 1.
Further, if value-at-risk McombinedMore than threshold value, then it is evaluated as high risk, if value-at-risk McombinedLess than etc. In threshold value, then low-risk is evaluated as.
In a kind of embodiment, if value-at-risk McombinedMore than -0.397, then it is evaluated as high risk, if value-at-risk McombinedLess than or equal to -0.397, then low-risk is evaluated as.
The sixth aspect of the present invention provides a kind of Prognosis in Breast Cancer apparatus for evaluating, including:
Prognosis in Breast Cancer value-at-risk McombinedComputing module, for calculating Prognosis in Breast Cancer value-at-risk Mcombined, described Mcombined=-0.69x SAge+0.62x SMenopausal Status–1.24x S PR status+0.85x SLymph node status- 0.74x SIATG5–0.74x SFIP200
Prognosis in Breast Cancer risk evaluation module, for according to value-at-risk McombinedAssess Prognosis in Breast Cancer risk.
Further, SAgeIt refer to the variate-value divided according to the age of patient.
In a kind of embodiment, if the age of patient is more than 50 years old, SAgeValue is 2, if the age of patient is less than Or it is equal to 50 years old, then SAgeValue is 1.
Further, SMenopausal StatusBe according to patient whether menopause divide variate-value.
In a kind of embodiment, if patient's menopause, SMenopausal StatusValue is 2, if the non-menopause of patient, Then SMenopausal StatusValue is 1.
Further, SPR statusIt is the variate-value divided according to the progesterone receptor status of patient.
In a kind of embodiment, if the progesterone receptor status of patient is the positive, SPR statusValue is 2, if The progesterone receptor status of patient is feminine gender, then SPR statusValue is 1.The yin and yang attribute of progesterone receptor status divides, and belongs to The prior art is divided according to method in the prior art.
Further, SLymph node statusIt is to be drawn according to whether the breast cancer cell of patient is transferred into lymph node The variate-value divided.
In a kind of embodiment, if the breast cancer cell of patient is transferred into lymph node, SLymph node statusIt takes Value is 2, if the breast cancer cell of patient is not diverted into lymph node, SLymph node statusValue is 1.
Further, SIATG5Refer to the SI (staining according to the immunohistochemical staining of the breast cancer tissue of patient Index the variate-value) divided.The numberical range of SI is 0~9.
Specifically, in a kind of embodiment, score value proportional SI=staining power score values x, those skilled in the art can Rule of thumb range estimation judges staining power being divided into four different grades, when staining power is negative, staining power score value It is 0, when staining power is weak, staining power score value is 1;When staining power is middle, staining power score value is 2;Work as dyeing When intensity is strong, staining power score value is 3, and proportional score value is divided by the cell accounting being colored, when what is be colored When cell accounting is 0-10%, proportional score value is 1, when the cell accounting being colored is 10%-50%, proportional point Value is 2, and when the cell accounting being colored is 50% or more, proportional score value is 3.
Further, SFIP200It is positive according to the FIP200 of the breast cancer tissue of patient expression to refer to or feminine gender divides Variate-value.
In a kind of embodiment, as long as there is FIP200 expression in nucleus, then regard as being that FIP200 expression is positive, instead To be identified as FIP200 expression negative, when FIP200 is expressed it is positive when, SFIP200Value be 2, when FIP200 express it is negative When, SFIP200Value be 1.
Further, if value-at-risk McombinedMore than threshold value, then it is evaluated as high risk, if value-at-risk McombinedLess than etc. In threshold value, then low-risk is evaluated as.
In a kind of embodiment, if value-at-risk McombinedMore than -0.397, then it is evaluated as high risk, if value-at-risk McombinedLess than or equal to -0.397, then low-risk is evaluated as.
Compared with prior art, the beneficial effects of the present invention are:
Inventor find by detect sample in ATG5 and FIP200 expression, can recognize that ATG5 and The sample of FIP200 low expressions, and can further predict such sample for the poor type of high risk, prognosis.In addition, through 200 The expression data and survival number of breast cancer patients sample, can be effective it is demonstrated that by the characterization of ATG5 and FIP200 expression quantity Ground predicts the sample of high risk, poor prognosis, it is seen that drugs or examination of the ATG5 and FIP200 in preparation or Screening Diagnosis breast cancer The use of agent box or the drug of screening treatment breast cancer has high industrial utilization on the way.
Description of the drawings
Fig. 1:It is shown as the photograph of the immunohistochemical staining 100X and 400X of the ATG5 of the malignant cell of breast cancer tissue's sample Piece, staining power are divided into four grades, and Score 0 indicates that negative (negative), Score 1 indicate weak (weak), Score 2 In expression (moderate), Score 3 is indicated strong (strong).
Fig. 2:It is shown as the immunohistochemical staining 100X's and 400X of the FIP200 of the malignant cell of breast cancer tissue's sample The expression of photo, FIP200 is divided into three grades:Cytoplasm-/nuclei- (Grade I), cytoplasm+/nuclei- (Grade II), cytoplasm+/nuclei+ (Grade III), cytoplasm-/nuclei+ (Grade III), wherein Grade I and Grade II indicate negative, and Grade III indicate positive.
Fig. 3 is shown as the survival analysis curve of ATG5+ (n=81) and ATG5- (n=119), it can be seen that the high table of ATG5 Up to implying better breast cancer disease-free survival.
Fig. 4 is shown as the survival analysis curve of FIP200+ (n=72) and FIP200- (n=128), it can be seen that FIP200 High expression show better breast cancer disease-free survival.
Fig. 5 is shown as ATG5+/FIP200+ (n=30), ATG5+/FIP200- (n=51), ATG5-/FIP200+ (n= 42) and the survival analysis curve of ATG5-/FIP200- (n=77), it can be seen that ATG5+/FIP200+'s the result is that best.
Fig. 6:Be shown as 3 years DFS (disease free survival) ROC curve, two curves carry respectively The comparison of the model of ATG5 and FIP200 expression and the model without above two protein.
Fig. 7:Be shown as 5 years DFS (disease free survival) ROC curve, two curves carry respectively The comparison of the model of ATG5 and FIP200 expression and the model without above two protein.
Fig. 8 is shown as according to model:Mcombined=-0.69x Age+0.62x Menopausal Status -1.24x PR 200 patients are divided into high risk by status+0.85x Lymph node status-0.74x ATG5-0.74x FIP200 (n=84) the survival analysis curve made with low-risk (n=116).
Specific implementation mode
Illustrate that embodiments of the present invention, those skilled in the art can be by this specification below by way of specific specific example Disclosed content understands the further advantage and effect of the present invention easily.The present invention can also pass through in addition different specific realities The mode of applying is embodied or practiced, the various details in this specification can also be based on different viewpoints with application, without departing from Various modifications or alterations are carried out under the spirit of the present invention.
Before further describing the specific embodiments of the present invention, it should be appreciated that protection scope of the present invention is not limited to down State specific specific embodiment;It is also understood that the term used in the embodiment of the present invention is specific specific in order to describe Embodiment, the protection domain being not intended to be limiting of the invention;In description of the invention and claims, unless in text In addition explicitly point out, singulative "one", " one " and " this " include plural form.
When embodiment provides numberical range, it should be appreciated that except non-present invention is otherwise noted, two ends of each numberical range Any one numerical value can be selected between point and two endpoints.Unless otherwise defined, in the present invention all technologies for using and Scientific terminology is identical as the normally understood meaning of those skilled in the art of the present technique.Except used in embodiment specific method, equipment, Outside material, the record according to those skilled in the art to the grasp of the prior art and the present invention can also use and this Any method, equipment and the material of the similar or equivalent prior art of method, equipment described in inventive embodiments, material come real The existing present invention.
Unless otherwise stated, disclosed in this invention experimental method, detection method, preparation method be all made of this technology neck Molecular biology, biochemistry, chromatin Structure and the analysis of domain routine, analytical chemistry, cell culture, recombinant DNA technology and The routine techniques of related field.These technologies existing perfect explanation in the prior art, for details, reference can be made to the MOLEC such as Sambrook μLAR CLONING:A LABORATORY MANUAL, Second edition, Cold Spring Harbor Laboratory Press, 1989and Third edition, 2001;Ausubel etc., CURRENT PROTOCOLS IN MOLEC μ LAR BIOLOGY, John Wiley&Sons, New York, 1987and periodic updates;the series METHODS IN ENZYMOLOGY, Academic Press, San Diego;Wolffe, CHROMATIN STRUCTURE AND FUNCTION, Third edition, Academic Press, San Diego, 1998;METHODS IN ENZYMOLOGY, Vol.304, Chromatin (P.M.Wassarman and A.P.Wolffe, eds.), Academic Press, San Diego, 1999;With METHODS IN MOLEC μ LAR BIOLOGY, Vol.119, Chromatin Protocols (P.B.Becker, ed.) Humana Press, Totowa, 1999 etc..
Embodiment 1
Get out the paraffin section of breast cancer tissue.
Two step method immunohistochemical kit (GTVision is used to these samplesTMIII) to ATG5 therein and FIP200 It is dyed.The detection of ATG5 be rabbit anti-ATG5 polyclonal antibodies 10181-2-AP (Proteintech Group, Chicago,IL,USA).The detection of FIP200 be rabbit anti-FIP200 polyclonal antibodies 16172-1-AP (Proteintech Group,Chicago,IL,USA).Negative control replaces main antibody with phosphate buffer solution.By stone Wax slice is dipped in dimethylbenzene 5 minutes, 3 times.Slice is taken out to be placed in 100% absolute ethyl alcohol 3 minutes, 2 times;It is placed in successively Each 3 minutes of 90%-70% alcohol at different levels.It is rinsed 3 times, every time 3 minutes with PBS.Antibody incubation after ten minutes, by that will be sliced 0.01M Tris-sodium citrate buffer boil 20 minutes extraction antigen at 121 degrees Celsius.For ATG5 and FIP200 has carried out the processing of confining liquid incubation in 20 minutes to eliminate endogenous peroxidase activity, then by its with it is anti- ATG5(1:Or anti-FIP200 (1 50):100) 4 degrees Celsius of overnight incubations of an antiantibody.
Classify to coloration result.
The sxemiquantitative classification Main Basiss staining index (SI) of ATG5.The computational methods of SI are:SI=dyeing is strong Degree score value is multiplied by proportional score value.As shown in Figure 1, those skilled in the art can rule of thumb estimate judgement, by staining power It is divided into four grades:Score 0, Score 1, Score 2 and Score 3, Score 0 are indicated:When staining power is feminine gender (negative) when, staining power score value indicates for 0, Score 1:When staining power is weak (weak), staining power score value It is indicated for 1, Score 2:In staining power is when (moderate), staining power score value indicates for 2, Score 3:Work as dyeing When intensity is strong (strong), staining power score value is 3.Proportional score value is divided by the cell accounting being colored, when When the cell accounting being colored is 0-10%, proportional score value is 1, when the cell accounting being colored is 10%-50%, at The score value of ratio is 2, and when the cell accounting being colored is 50% or more, proportional score value is 3.The numberical range of SI (range) it is 0-9, SI is defined as ATG5+positive staining more than or equal to 5, and SI is defined as ATG5- less than 5 negtive staining。
As shown in Fig. 2, the expression grade of FIP200 is divided into three classes:
Cytoplasm-/nuclei- (Grade I) also just says when being expressed without FIP200 in cytoplasm and nucleus, It is denoted as Grade I;
Cytoplasm+/nuclei- (Grade II), that is to say, that have in cytoplasm in FIP200 expression, nucleus and do not have When having FIP200 expression, it is denoted as Grade II;
Cytoplasm+/nuclei+ (Grade III), that is to say, that having in cytoplasm in FIP200 expression, nucleus has When FIP200 is expressed, it is denoted as Grade III;
Cytoplasm-/nuclei+ (Grade III), that is to say, that do not have in cytoplasm in FIP200 expression, nucleus When having FIP200 expression, it is denoted as Grade III.
The FIP200 expression quantity of Grade III is defined as positive (positive) that is, FIP200+, Grade I or II For negative (negative) that is, FIP200-.
The paraffin section sample of the breast cancer tissue of 200 breast cancer patients is got out, various kinds is analyzed using the above method ATG5 and FIP200 expression quantity in this.
200 breast cancer disease human breast carcinoma tissue samples are divided into ATG5+ and ATG5- two according to the expression of ATG5 Class is defined as ATG5+ wherein there is the SI of the breast cancer tissue of 81 breast cancer patients to be more than or equal to 5;Remaining 119 mammary gland The SI of the breast cancer tissue of carninomatosis people is less than 5, is defined as ATG5-.Pass through R packets " survival " generate ATG5+ (n=81) and The survival analysis curve of ATG5- (n=119), as shown in Figure 3, it can be seen that the high expression of ATG5 implies better breast cancer Disease-free survival.
According to the expression of FIP200 by 200 breast cancer disease human breast carcinoma tissue samples be divided into FIP200+ with Two classes of FIP200-, wherein the breast cancer tissue of 71 breast cancer patients belongs to for FIP200+, other 128 breast cancer patients Breast cancer tissue belongs to FIP200-.Utilize R packets " survival " mappings, obtain FIP200+ (n=72) and FIP200- (n= 128) survival analysis curve, as shown in Figure 4, it can be seen that the high expression of FIP200 shows better breast cancer without diease occurrence It deposits.
According to the expression of ATG5 and FIP200,200 breast cancer disease human breast carcinoma tissue samples are divided into four classes: ATG5+/FIP200+, ATG5+/FIP200-, ATG5-/FIP200+, ATG5-/FIP200-, wherein 30 breast cancer disease human milks Adenocarcinoma tissue belongs to ATG5+/FIP200+, and 51 breast cancer disease human breast carcinoma tissues belong to ATG5+/FIP200-, 42 mammary gland Carninomatosis human breast carcinoma tissue belongs to ATG5-/FIP200+, remaining 77 breast cancer disease human breast carcinoma tissues belong to ATG5-/ FIP200-.Utilize R packets " survival " mappings, ATG5+/FIP200+ (n=30), ATG5+/FIP200- (n=51) are obtained, The survival analysis curve of ATG5-/FIP200+ (n=42) and ATG5-/FIP200- (n=77), as shown in Figure 5, it can be seen that ATG5+/FIP200+'s the result is that best.That is the high expression of ATG5 and FIP200 show best breast cancer without Diease occurrence is deposited.
Data do regression model through a large number of experiments, obtain Prognosis in Breast Cancer assessment models.
The first Prognosis in Breast Cancer assessment models is known as traditional model, the calculating of this prognosis evaluation model Formula is:
Mtraditional=-0.74x SAge+0.75x SMenopausal Status–1.06xS PR status+0.84x SLymph node status
Wherein, MtraditionalRefer to Prognosis in Breast Cancer value-at-risk, SAgeRefer to the variate-value divided according to the age of patient, If the age of patient is more than 50 years old, SAgeValue is 2, if the age of patient is less than or equal to 50 years old, SAgeValue is 1;SMenopausal StatusBe according to patient whether menopause divide variate-value, if patient's menopause, SMenopausal StatusIt takes Value is 2, if the non-menopause of patient, SMenopausal StatusValue is 1;SPR statusIt is the progesterone receptor shape according to patient The yin and yang attribute division of the variate-value that state divides, progesterone receptor status belongs to the prior art, if the progesterone receptor shape of patient State is the positive, then SPR statusValue is 2, if the progesterone receptor status of patient is feminine gender, SPR statusValue is 1; SLymph node statusIt is that the variate-value of lymph node division whether is transferred into according to the breast cancer cell of patient, if patient Breast cancer cell be transferred into lymph node, then SLymph node statusValue is 2, if the breast cancer cell of patient does not have It is transferred to lymph node, then SLymph node statusValue is 1.
By corresponding to the first Prognosis in Breast Cancer assessment models calculation formula and 200 breast cancer patients in it is disease-free S corresponding to breast cancer tissue's sample of the patient of existence 3 yearsAge、SMenopausal Status、S PR status、SLymph node statusVariate-value and disease-free survival time value are updated to R packets and generate ROC curve.As shown in the 6-1 curves in Fig. 6.
Second of Prognosis in Breast Cancer assessment models is known as combined model, the calculation formula of this prognosis evaluation model For:
Mcombined=-0.69x SAge+0.62x SMenopausal Status–1.24x S PR status+0.85x SLymph node status-0.74x SIATG5–0.74x SFIP200
Wherein, SAgeRefer to the variate-value divided according to the age of patient, if the age of patient is more than 50 years old, SAgeIt takes Value is 2, if the age of patient is less than or equal to 50 years old, SAgeValue is 1;SMenopausal StatusIt is whether exhausted according to patient Divided variate-value, if patient's menopause, SMenopausal StatusValue is 2, if the non-menopause of patient, SMenopausal StatusValue is 1;SPR statusIt is the variate-value divided according to the progesterone receptor status of patient, the moon of progesterone receptor status The positive, which divides, belongs to the prior art, if the progesterone receptor status of patient is the positive, SPR statusValue is 2, if suffered from The progesterone receptor status of person is feminine gender, then SPR statusValue is 1;SLymph node statusIt is thin according to the breast cancer of patient Whether born of the same parents are transferred into the variate-value that lymph node is divided, if the breast cancer cell of patient is transferred into lymph node, SLymph node statusValue is 2, if the breast cancer cell of patient is not diverted into lymph node, SLymph node statusValue It is 1;SIATG5Refer to being divided according to the SI (staining index) of the immunohistochemical staining of the breast cancer tissue of patient Variate-value, the numberical range of SI is 0~9, specifically, score value proportional SI=staining power score values x, people in the art Member, which can rule of thumb estimate, to be judged staining power being divided into four different ranks, when staining power is negative, staining power Score value is 0, and when staining power is weak, staining power score value is 1;When staining power is middle, staining power score value is 2;When When staining power is strong, staining power score value is 3, and proportional score value is divided by the cell accounting being colored, when being contaminated When the cell accounting of color is 0-10%, proportional score value is 1, proportional when the cell accounting being colored is 10%-50% Score value be 2, when the cell accounting being colored be 50% or more when, proportional score value be 3;SFIP200Refer to according to patient's The FIP200 expression of breast cancer tissue is the positive or negative variate-value divided, as long as have FIP200 expression in nucleus, It then regards as being the FIP200 expression positives, otherwise is identified as FIP200 expression feminine genders, when FIP200 expresses the positive, SFIP200 Value be 2, when FIP200 is expressed it is negative when, SFIP200Value be 1.
By corresponding to second of Prognosis in Breast Cancer assessment models calculation formula and 200 breast cancer patients in it is disease-free S corresponding to breast cancer tissue's sample of the patient of existence 3 yearsAge、SMenopausal Status、S PR status、SLymph node status、SIATG5And SFIP200Variate-value and disease-free survival time value are updated to R packets and generate ROC curve.As the 6-2 in Fig. 6 is bent Shown in line.By the comparison of 6-1 curves and 6-2 curves, can absolutely prove:Second of prognosis evaluation model is better than the first prognosis Assessment models.
Similarly, with reference to the above method, by the calculation formula and 200 corresponding to the first Prognosis in Breast Cancer assessment models S in example breast cancer patients corresponding to breast cancer tissue's sample of 5 years patients of disease-free survivalAge、SMenopausal Status、S PR status、SLymph node statusVariate-value and disease-free survival time value are updated to R packets and generate ROC curve.Such as the 7-1 in Fig. 7 Shown in curve.
By corresponding to second of Prognosis in Breast Cancer assessment models calculation formula and 200 breast cancer patients in it is disease-free S corresponding to breast cancer tissue's sample of the patient of existence 5 yearsAge、SMenopausal Status、S PR status、SLymph node status、SIATG5And SFIP200Variate-value and disease-free survival time value are updated to R packets and generate ROC curve.As the 7-2 in Fig. 7 is bent Shown in line.By the comparison of 7-1 curves and 7-2 curves, can absolutely prove:It can absolutely prove:Second of prognosis evaluation model is excellent In the first prognosis evaluation model.
Embodiment 2
It is found by embodiment 1, second of Prognosis in Breast Cancer assessment models is better than the first Prognosis in Breast Cancer assessment models. Specifically, second of Prognosis in Breast Cancer assessment models is known as combined model, the calculation formula of this prognosis evaluation model For:
Mcombined=-0.69x SAge+0.62x SMenopausal Status–1.24x S PR status+0.85x SLymph node status-0.74x SIATG5–0.74x SFIP200
Wherein, SAgeRefer to the variate-value divided according to the age of patient, if the age of patient is more than 50 years old, SAgeIt takes Value is 2, if the age of patient is less than or equal to 50 years old, SAgeValue is 1;SMenopausal StatusIt is whether exhausted according to patient Divided variate-value, if patient's menopause, SMenopausal StatusValue is 2, if the non-menopause of patient, SMenopausal StatusValue is 1;SPR statusIt is the variate-value divided according to the progesterone receptor status of patient, the moon of progesterone receptor status Property sun division belong to the prior art, if the progesterone receptor status of patient be the positive, SPR statusValue is 2, if suffered from The progesterone receptor status of person is feminine gender, then SPR statusValue is 1;SLymph node statusIt is thin according to the breast cancer of patient Whether born of the same parents are transferred into the variate-value that lymph node is divided, if the breast cancer cell of patient is transferred into lymph node, SLymph node statusValue is 2, if the breast cancer cell of patient is not diverted into lymph node, SLymph node statusValue It is 1;SIATG5Refer to being divided according to the SI (staining index) of the immunohistochemical staining of the breast cancer tissue of patient Variate-value, the numberical range of SI is 0~9, specifically, score value proportional SI=staining power score values x, people in the art Member, which can rule of thumb estimate, to be judged staining power being divided into four different ranks, when staining power is negative, staining power Score value is 0, and when staining power is weak, staining power score value is 1;When staining power is middle, staining power score value is 2;When When staining power is strong, staining power score value is 3, and proportional score value is divided by the cell accounting being colored, when being contaminated When the cell accounting of color is 0-10%, proportional score value is 1, proportional when the cell accounting being colored is 10%-50% Score value be 2, when the cell accounting being colored be 50% or more when, proportional score value be 3;SFIP200Refer to according to patient's The FIP200 expression of breast cancer tissue is the positive or negative variate-value divided, as long as have FIP200 expression in nucleus, It then regards as being the FIP200 expression positives, otherwise is identified as FIP200 expression feminine genders, when FIP200 expresses the positive, SFIP200 Value be 2, when FIP200 is expressed it is negative when, SFIP200Value be 1.McombinedValue-at-risk is represented, the threshold value of value-at-risk is (also That is Cutoff)
It is -0.397, if value-at-risk is more than -0.397, is evaluated as high risk, if value-at-risk is less than or equal to -0.397, Then it is evaluated as low-risk.
By the S corresponding to breast cancer tissue's sample of 200 breast cancer patientsAge、SMenopausal Status、S PR status、 SLymph node status、SIATG5And SFIP200Variate-value substitutes into second of Prognosis in Breast Cancer assessment models respectively, calculates outlet air Danger value, and it is high risk or low-risk to assess.
As a result, there is 116 to be evaluated as low-risk in 200 samples, 84 Samples Estimates are high risk.Then 116 are made The DFS curves of example sample, as shown in 8-1 curves in Fig. 8.The DFS curves of 84 samples, as shown in 8-2 curves in Fig. 8.Pass through Fig. 8 can be clearly seen that being evaluated as the case of low-risk its Survival is better than the case for being evaluated as high risk, with practical feelings Condition is consistent.
Above embodiment is can not to be interpreted as the limit to the present invention in order to illustrate embodiment disclosed by the invention System.In addition, in various modifications and invention listed herein method, composition variation, do not departing from the scope of the present invention Be obvious for those skilled in the art under the premise of spirit.Although having combined, the present invention's is a variety of specific Preferred embodiment has carried out specific description to the present invention, it is to be understood that, the present invention should not be limited only to these specific embodiments. In fact, various, obviously modification all should include to obtain invention for those skilled in the art as described above Within the scope of the invention.

Claims (14)

1.ATG5 albumen combines the purposes for being used to prepare or screening Prognosis in Breast Cancer assessment reagent with FIP200 albumen.
2. purposes of the reagent of specific recognition ATG5 albumen and FIP200 albumen in preparing Prognosis in Breast Cancer assessment kit.
3. a kind of Prognosis in Breast Cancer assesses kit, at least contain specific recognition ATG5 albumen and FIP200 in the kit The reagent of albumen.
4.ATG5 albumen combines the purposes that marker is assessed as Prognosis in Breast Cancer with FIP200 albumen.
5. a kind of Prognosis in Breast Cancer appraisal procedure, includes the following steps:
(1) Prognosis in Breast Cancer value-at-risk M is calculatedcombined, the Mcombined=-0.69x SAge+0.62x SMenopausal Status– 1.24x SPR status+0.85x SLymph node status-0.74x SIATG5–0.74x SFIP200, SAgeIt refer to the year according to patient The variate-value that age divides, SMenopausal StatusBe according to patient whether menopause divide variate-value, SPR statusIt is according to patient Progesterone receptor status divide variate-value, SLymph node statusIt is whether transferred according to the breast cancer cell of patient The variate-value divided to lymph node, SIATG5Refer to the SI institutes according to the immunohistochemical staining of the breast cancer tissue of patient The variate-value of division;
(2) according to value-at-risk McombinedAssess Prognosis in Breast Cancer risk.
6. a kind of Prognosis in Breast Cancer apparatus for evaluating, including:
Prognosis in Breast Cancer value-at-risk McombinedComputing module, for calculating Prognosis in Breast Cancer value-at-risk Mcombined, the Mcombined =-0.69x SAge+0.62x SMenopausal Status–1.24x SPR status+0.85x SLymph node status-0.74x SIATG5–0.74x SFIP200, SAgeRefer to the variate-value divided according to the age of patient, SMenopausal StatusIt is to be according to patient The variate-value that no menopause divides, SPR statusIt is the variate-value divided according to the progesterone receptor status of patient, SLymph node statusIt is whether the variate-value that lymph node is divided, SI are transferred into according to the breast cancer cell of patientATG5Refer to according to trouble The variate-value that the SI of the immunohistochemical staining of the breast cancer tissue of person is divided;
Prognosis in Breast Cancer risk evaluation module, for according to value-at-risk McombinedAssess Prognosis in Breast Cancer risk.
7. Prognosis in Breast Cancer apparatus for evaluating according to claim 6, which is characterized in that further include any in following characteristics Item or multinomial, proportional (1) described SI=staining powers score value x score value, when staining power is negative, staining power score value It is 0, when staining power is weak, staining power score value is 1;When staining power is middle, staining power score value is 2;Work as dyeing When intensity is strong, staining power score value is 3, and proportional score value is divided by the cell accounting being colored, when what is be colored When cell accounting is 0-10%, proportional score value is 1, when the cell accounting being colored is 10%-50%, proportional point Value is 2, and when the cell accounting being colored is 50% or more, proportional score value is 3;(2) as long as having in nucleus FIP200 is expressed, then regards as being that FIP200 expression is positive, otherwise it is negative to be identified as FIP200 expression.
8. Prognosis in Breast Cancer apparatus for evaluating according to claim 6, which is characterized in that if value-at-risk McombinedMore than threshold Value, then be evaluated as high risk, if value-at-risk McombinedLess than or equal to threshold value, then low-risk is evaluated as.
9. a kind of Prognosis in Breast Cancer apparatus for evaluating, described device include computer, the computer is programmed to execute as follows Step:
(1) Prognosis in Breast Cancer value-at-risk M is calculatedcombined, the Mcombined=-0.69x SAge+0.62x SMenopausal Status– 1.24x SPR status+0.85x SLymph node status-0.74x SIATG5–0.74x SFIP200, SAgeIt refer to the year according to patient The variate-value that age divides, SMenopausal StatusBe according to patient whether menopause divide variate-value, SPR statusIt is according to patient Progesterone receptor status divide variate-value, SLymph node statusIt is whether transferred according to the breast cancer cell of patient The variate-value divided to lymph node, SIATG5Refer to the SI institutes according to the immunohistochemical staining of the breast cancer tissue of patient The variate-value of division;
(2) according to value-at-risk McombinedAssess Prognosis in Breast Cancer risk.
10. Prognosis in Breast Cancer apparatus for evaluating according to claim 9, which is characterized in that further include appointing in following characteristics One or more, proportional (1) described SI=staining powers score value x score values, when staining power is negative, staining power point Value is 0, and when staining power is weak, staining power score value is 1;When staining power is middle, staining power score value is 2;Work as dye When intensity of colour is strong, staining power score value is 3, and proportional score value is divided by the cell accounting being colored, when being colored Cell accounting be 0-10% when, proportional score value be 1, when the cell accounting being colored be 10%-50% when, it is proportional Score value is 2, and when the cell accounting being colored is 50% or more, proportional score value is 3;(2) as long as having in nucleus FIP200 is expressed, then regards as being that FIP200 expression is positive, otherwise it is negative to be identified as FIP200 expression.
11. Prognosis in Breast Cancer apparatus for evaluating according to claim 9, which is characterized in that if value-at-risk McombinedMore than threshold Value, then be evaluated as high risk, if value-at-risk McombinedLess than or equal to threshold value, then low-risk is evaluated as.
12. a kind of computer readable storage medium being stored with computer program, the computer program makes computer execute such as Lower step:
(1) Prognosis in Breast Cancer value-at-risk M is calculatedcombined, the Mcombined=-0.69x SAge+0.62x SMenopausal Status– 1.24x SPR status+0.85x SLymph node status-0.74x SIATG5–0.74x SFIP200, SAgeIt refer to the year according to patient The variate-value that age divides, SMenopausal StatusBe according to patient whether menopause divide variate-value, SPR statusIt is according to patient Progesterone receptor status divide variate-value, SLymph node statusIt is whether transferred according to the breast cancer cell of patient The variate-value divided to lymph node, SIATG5Refer to the SI institutes according to the immunohistochemical staining of the breast cancer tissue of patient The variate-value of division;
(2) according to value-at-risk McombinedAssess Prognosis in Breast Cancer risk.
13. the computer readable storage medium according to claim 12 for being stored with computer program, which is characterized in that
(1) score value proportional the SI=staining powers score value x, when staining power is negative, staining power score value is 0, When staining power is weak, staining power score value is 1;When staining power is middle, staining power score value is 2;Work as staining power When being strong, staining power score value is 3, and proportional score value is divided by the cell accounting being colored, when the cell being colored When accounting is 0-10%, proportional score value is 1, and when the cell accounting being colored is 10%-50%, proportional score value is 2, when the cell accounting being colored is 50% or more, proportional score value is 3;(2) as long as there is FIP200 tables in nucleus It reaches, then regards as being that FIP200 expression is positive, otherwise it is negative to be identified as FIP200 expression.
14. Prognosis in Breast Cancer apparatus for evaluating according to claim 12, which is characterized in that if value-at-risk McombinedMore than threshold Value, then be evaluated as high risk, if value-at-risk McombinedLess than or equal to threshold value, then low-risk is evaluated as.
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110187107A (en) * 2019-04-26 2019-08-30 温州医科大学 A kind of prognostic evaluation of colorectal carcinoma device and method established based on tumor tissues infiltration immunocyte feature
CN112852968A (en) * 2021-04-08 2021-05-28 杨文琳 Triple negative breast cancer risk prediction method based on immune-related lncRNA

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110187107A (en) * 2019-04-26 2019-08-30 温州医科大学 A kind of prognostic evaluation of colorectal carcinoma device and method established based on tumor tissues infiltration immunocyte feature
CN112852968A (en) * 2021-04-08 2021-05-28 杨文琳 Triple negative breast cancer risk prediction method based on immune-related lncRNA

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