CN113249491A - Biomarker for diagnosing endometrial cancer and product and application thereof - Google Patents

Biomarker for diagnosing endometrial cancer and product and application thereof Download PDF

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CN113249491A
CN113249491A CN202110761222.5A CN202110761222A CN113249491A CN 113249491 A CN113249491 A CN 113249491A CN 202110761222 A CN202110761222 A CN 202110761222A CN 113249491 A CN113249491 A CN 113249491A
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eif3e
tmsb10
pdia6
biomarkers
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陈镘如
梅立
廖治
李延
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Sichuan Peoples Hospital of Sichuan Academy of Medical Sciences
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Abstract

The invention discloses a biomarker for diagnosing endometrial cancer, a product and an application thereof, and provides an application of a reagent for detecting biomarkers TMSB10, EIF3E and PDIA6 in a sample to be detected in preparation of a product for diagnosing and/or assisting in diagnosing endometrial cancer.

Description

Biomarker for diagnosing endometrial cancer and product and application thereof
Technical Field
The invention belongs to the field of biology and medicine, and particularly relates to a biomarker for diagnosing endometrial cancer, more particularly to a biomarker for diagnosing endometrial cancer, and a product and application thereof.
Background
Endometrial Cancer (UCEC), a kind of endometrial epithelial tumors derived from abnormal proliferation of endometrial cells, is also a female reproductive system malignancy with a high incidence rate, poses a serious threat to the health of women all over the world, and about 5 million women die worldwide each year from UCEC (Onstad MA, Schmantt RE, Lu KH. addressing the role of infection in the end clinical cancer k, preservation, and patent. J Clin Oncol,2016,34(35): 4225-. UCEC account for approximately 20% -30% of female reproductive tumors, and have a second incidence to cervical Cancer (Siegel RL, Miller KD, Jemal A. Cancer statistics,2017[ J ]. CA Cancer J Clin,2017,67(1): 7-30.). UCEC occurs in postmenopausal women, and it is possible that the secretion level of estrogen is unstable after menopause, and in addition, smoking, hypertension, overweight, genetic diseases, etc. may cause UCEC. The UCEC is mainly composed of two types, type I: is driven by hormone, and has good prognosis; type II: hormone independence, but poor prognosis (mountain P, Leary A, Creutzberg C, et al, endogenous cancer. Lancet,2016,387(10023): 1094-1108).
It has been shown that protein arginine methyltransferase 6(PRMT6) can promote the development of UCEC (Jiang N, Li QL, Pan W, et al. PRMT6 proteins endometeric cancer via AKT/mTOR signaling and indicators pore protein. int J Biochem Cell Biol,2020,120: 105681); the up-regulation of LINC01123 has significant relevance to the clinical progress and poor prognosis of UCEC patients (Yang Y, Wu J, Zhou H, et al, STATT 1-induced upper regulation of lncRNA LINC01123 precursors point or gnosis and proteins of progression of end cancer through miR-516b/KIF4A. cell Cycle,2020,19(12):1502-1516), but the molecular mechanism of UCEC development is not completely clear so far, and further, no effective method for early diagnosis of endometrial cancer exists, the diagnosis of endometrial cancer at present is mainly determined according to the disease history, clinical examination, pathological examination and various auxiliary examination results of a subject, and the main detection method comprises the following steps: b-ultrasonic examination, diagnostic uterine curettage, hysteroscopy and lymphography, which have the defects of low detectable rate, easy severe physiological pain to patients and the like.
Therefore, research on specific biomarkers related to endometrial cancer and capable of being used for early diagnosis of endometrial cancer is of great significance for revealing the occurrence and development mechanism of endometrial cancer, early diagnosis of endometrial cancer or prediction of the risk of endometrial cancer.
Disclosure of Invention
In view of the above, in view of the above-mentioned deficiencies of the current detection technologies in the field, the present invention screens out the differentially expressed genes TMSB10, EIF3E and PDIA6 related to endometrial cancer, and further the results of the diagnostic efficacy test show that the combination of TMSB10, EIF3E and PDIA6 can be used as a biomarker for endometrial cancer, so that the early diagnosis of the endometrial cancer and the risk of the endometrial cancer in the subject can be performed according to the combination of TMSB10, EIF3E and PDIA 6.
The above object of the present invention is achieved by the following technical solutions:
in a first aspect, the invention provides the use of a biomarker in the manufacture of a product for diagnosing or prognosing early stage endometrial cancer.
Further, the biomarkers include TMSB10, EIF3E, PDIA 6;
preferably, the biomarker TMSB10 is up-regulated in endometrial cancer;
preferably, the biomarker EIF3E is down-regulated in endometrial cancer;
preferably, the biomarker PDIA6 is upregulated in endometrial cancer.
"TMSB 10" as used herein means a Gene having Gene ID of 9168 located in the 1-band and 2-subband in the 1-region of the short arm of chromosome 2.
"EIF 3E" as used herein refers to a Gene having Gene ID 3646 located in 3-band 1 of long arm 2 region of chromosome 8.
The term "PDIA 6" as used herein refers to a Gene having Gene ID of 10130, which is located in the 5-band 1 of the short arm 2 region of chromosome 2.
Further, the product comprises reagents to detect the presence, absence and/or amount of the biomarkers TMSB10, EIF3E, PDIA6 or functional fragments thereof in the sample.
Further, the reagents include reagents for detecting the presence, absence and/or amount of the biomarkers TMSB10, EIF3E, PDIA6 or functional fragments thereof in a sample using digital imaging techniques, protein immunization techniques, dye techniques, nucleic acid sequencing techniques, nucleic acid hybridization techniques, chromatography techniques, mass spectrometry techniques;
preferably, the reagents for detecting the presence, absence and/or amount of the biomarkers TMSB10, EIF3E, PDIA6 or functional fragments thereof in a sample using protein immunoassay techniques include antibodies;
more preferably, the antibody is a labeled antibody specific for an epitope of the biomarkers TMSB10, EIF3E, PDIA6 or functional fragments thereof;
preferably, the reagent for detecting the presence, absence and/or amount of the biomarkers TMSB10, EIF3E, PDIA6 or functional fragments thereof in the sample using dye technology comprises a dye;
more preferably, the dye is a dye specific for the biomarkers TMSB10, EIF3E, PDIA6 or functional fragments thereof;
preferably, the reagents for detecting the presence, absence and/or amount of the biomarkers TMSB10, EIF3E, PDIA6 or functional fragments thereof in a sample using nucleic acid sequencing technology comprise primers;
more preferably, the primer is a primer that binds to the sequence of the biomarker TMSB10, EIF3E, PDIA6, or a functional fragment thereof;
preferably, the reagents for the presence, absence and/or amount of the biomarkers TMSB10, EIF3E, PDIA6 or functional fragments thereof in a sample using nucleic acid hybridization techniques comprise probes;
more preferably, the probe is a labeled probe complementary to the sequence of the biomarkers TMSB10, EIF3E, PDIA6 or a functional fragment thereof.
Further, the sample comprises body fluid, tissue;
preferably, the bodily fluid comprises blood, plasma, serum, lymph, urine, serosal cavity fluid, spinal fluid, synovial fluid, aqueous humor, tears, saliva.
Further, the tissue sample comprises a tissue sample of a lesion site.
Further, the primer can be prepared by chemical synthesis, i.e., by appropriately designing with reference to known information using a method well known to those skilled in the art, and by chemical synthesis.
Further, the probe may be prepared by chemical synthesis, i.e., by appropriately designing with reference to known information using a method well known to those skilled in the art, and by means of chemical synthesis, or may be prepared by preparing a gene containing a desired nucleic acid sequence from a biological material and amplifying it using a primer designed for amplifying the desired nucleic acid sequence.
The term "primer" used in the present invention means 7 to 50 nucleic acid sequences capable of forming a Base pair complementary to a template strand (Base pair) and serving as a starting point for copying the template strand, and the primer is usually synthesized, but a naturally occurring nucleic acid may be used, and the sequence of the primer is not necessarily completely identical to the sequence of the template, and may be mixed with additional features that do not change the basic properties of the primer as long as it is sufficiently complementary to be able to hybridize with the template, and examples of the additional features that may be mixed include methylation, capping, substitution of one or more nucleic acids with a homolog, and modification between nucleic acids, but are not limited thereto.
The term "probe" used in the present invention refers to a single-stranded nucleic acid having a known nucleotide sequence, which has a nucleotide sequence structure substantially complementary to a target nucleic acid and can form a complementary double strand with the target nucleic acid, wherein the probe can carry a label, for example, the label can be attached to the 5 'end or 3' end of the probe, the length of the probe is not limited as long as specific hybridization and specific binding with the target nucleotide sequence are achieved, and any length can be used, the length of the probe can be as short as 25, 20, 15, 13 or 10 base pairs, and likewise, the length of the probe can be as long as 60, 80, 100, 150, 300 base pairs or more, even the whole gene, and the length of the probe is usually at least 14 base pairs and at most usually not more than 30 base pairs because different probe lengths have different effects on hybridization efficiency and signal specificity, the length of complementarity to the nucleotide sequence of interest is preferably 15-25 base pairs, and the probe self-complementary sequence is preferably less than 4 base pairs, so as not to affect hybridization efficiency.
The term "antibody" as used herein refers to a labeled antibody specific for an epitope of the biomarkers TMSB10, EIF3E, PDIA6 or functional fragments thereof, such as monoclonal antibodies, polyclonal antibodies, antibodies with polyepitopic specificity, single chain antibodies, multispecific antibodies, and antibody fragments, which may be chimeric, humanized, human, and synthetic.
The term "biomarker," as used herein, refers to a molecular indicator with a specific biological property, biochemical characteristic, or other characteristic that can be used to determine the presence or absence of a particular disease or condition and/or the severity of a particular disease or condition.
In a second aspect of the invention, there is provided a product for diagnosing or prognosing early stage endometrial cancer.
Further, the product comprises reagents to detect the biomarkers TMSB10, EIF3E, PDIA6, or functional fragments thereof;
preferably, the product comprises a detection kit, a chip and test paper.
Further, the detection kit comprises primers and/or probes for detecting the biomarkers TMSB10, EIF3E, PDIA6 or functional fragments thereof;
preferably, the detection kit further comprises a reagent for detecting an internal reference gene;
more preferably, the reagent for detecting the internal reference gene comprises a primer and/or a probe aiming at the internal reference gene;
preferably, the detection kit further comprises dNTPs and Mg2+Ions, DNA polymerase or DNA polymerase containing dNTPs, Mg2+Ion, DNA polymerizationA PCR system of enzymes;
preferably, the detection kit further comprises a bisulfite or hydrazine salt.
Further, the detection kit further comprises (but is not limited to): quality control products, negative control and/or instructions for using the detection kit.
The term "chip", also referred to as "array", as used herein, refers to a solid support comprising attached nucleic acid or peptide probes, the array typically comprising a plurality of different nucleic acid or peptide probes attached to a substrate surface at different known locations, these arrays also being referred to as "microarrays", which arrays can be generated typically by using a mechanosynthesis method or a light-guided synthesis method, which is a combination method combining photolithography and solid phase synthesis methods, the arrays can comprise flat surfaces, or can be nucleic acids or peptides on beads, gels, polymer surfaces, fibers such as optical fibers, glass or any other suitable substrate, which arrays can be packaged in a manner that allows for diagnostic or other manipulation of a fully functional device.
The term "strip" used in the present invention includes a strip carrier and an oligonucleotide immobilized on the strip carrier, which is capable of detecting the expression level of the biomarkers TMSB10, EIF3E, PDIA6 or functional fragments thereof.
The third aspect of the invention provides an application of a reagent for detecting the biomarkers TMSB10, EIF3E, PDIA6 or functional fragments thereof in preparing a product for diagnosing or predicting early endometrial cancer.
In a fourth aspect of the invention, there is provided a detection system or device for diagnosing whether a subject has, or is at risk of, endometrial cancer.
Further, the detection system or apparatus comprises the following units:
(1) an analysis unit adapted to measure the amount of the biomarkers TMSB10, EIF3E, PDIA6 or functional fragments thereof in a sample of a subject;
(2) an evaluation unit comprising a stored reference and a data processor having implemented an algorithm for comparing the amount of the biomarkers TMSB10, EIF3E, PDIA6 measured by the analysis unit with the stored reference, thereby diagnosing whether endometrial cancer is present or at risk of endometrial cancer.
The invention also provides application of the biomarkers TMSB10, EIF3E and PDIA6 in construction of a calculation model for predicting endometrial cancer.
The fifth aspect of the invention provides the use of the biomarkers TMSB10, EIF3E, PDIA6 for the preparation of a pharmaceutical composition for the prevention and/or treatment of endometrial cancer;
preferably, the pharmaceutical composition comprises an inhibitor for inhibiting the expression level of TMSB10, a promoter for promoting the expression level of EIF3E, and an inhibitor for inhibiting the expression level of PDIA 6.
In a sixth aspect, the invention provides a method of screening for a candidate agent for the prevention and/or treatment of endometrial cancer.
Further, the method comprises the steps of:
(1) treating a system expressing or containing TMSB10, EIF3E, PDIA6 with a test substance;
(2) detecting the expression of TMSB10, EIF3E and PDIA6 in the system;
(3) test substances which can reduce the expression level of TMSB10, increase the expression level of EIF3E and reduce the expression level of PDIA6 are selected as candidate drugs.
Further, the system is selected from: a cell system, a subcellular system, a solution system, a tissue system, an organ system, or an animal system.
The invention has the advantages and beneficial effects that:
the invention firstly discovers the biomarker combinations TMSB10, EIF3E and PDIA6 which can be used for diagnosing the endometrial cancer, and further diagnostic efficacy verification results show that the combination of TMSB10, EIF3E and PDIA6 has better diagnostic efficacy, and whether a subject has the endometrial cancer or is at risk of having the endometrial cancer can be diagnosed according to the combination of TMSB10, EIF3E and PDIA 6.
Drawings
Embodiments of the invention are described in detail below with reference to the attached drawing figures, wherein:
FIG. 1 is a box plot showing differential expression of TMSB10 in the training set;
FIG. 2 is a boxplot showing the differential expression of EIF3E in the training set;
FIG. 3 is a boxplot showing differential expression of PDIA6 in the training set;
FIG. 4 is a box line plot showing differential expression of TMSB10 in the validation set;
FIG. 5 is a boxplot showing differential expression of EIF3E in validation set;
FIG. 6 shows a boxplot of the differential expression of PDIA6 in validation set;
FIG. 7 shows a graph of the ROC in the training set for TMSB 10;
FIG. 8 shows a graph of TMSB10 on a validation set ROC;
FIG. 9 shows a ROC plot of EIF3E in a training set;
FIG. 10 shows a ROC plot of EIF3E in the validation set;
FIG. 11 shows a ROC plot of PDIA6 in a training set;
FIG. 12 shows a ROC plot of PDIA6 in a validation set;
FIG. 13 shows ROC plots of TMSB10+ EIF3E + PDIA6 in combination in the training set for the diagnosis of endometrial cancer;
FIG. 14 shows ROC plots of TMSB10+ EIF3E + PDIA6 in combination in the validation set for diagnosing endometrial cancer.
Detailed Description
The present invention is further illustrated below with reference to specific examples, which are intended to be illustrative only and are not to be construed as limiting the invention. As will be understood by those of ordinary skill in the art: various changes, modifications, substitutions and alterations can be made to the embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the claims and their equivalents. The following examples are examples of experimental methods not indicating specific conditions, and the detection is usually carried out according to conventional conditions or according to the conditions recommended by the manufacturers.
Example 1 screening for genes differentially expressed in endometrial cancer
1. Data source
Endometrial Cancer (UCEC) data set GSE17025 was downloaded from the GEO database as a training set, sample size was Control: UCEC 12: 91;
endometrial cancer data (UCEC data) were downloaded from the TCGA database as a validation set, sample size was Control: UCEC 35: 543;
the raw data downloaded from the GEO database and the TCGA database are standardized, the standardized gene expression matrix is annotated by a Platform file, a plurality of probes correspond to the same gene, and the average value is taken as the expression quantity of the gene.
2. Differential expression analysis
And respectively carrying out differential expression analysis on the training set and the verification set by using a 'limma' packet in R language software, wherein the screening standard of differential expression genes is as follows: val <0.05, | logFC | > 1.
3. Results of the experiment
The results show that the intersection of the differentially expressed genes in the two data sets results in 67 common differentially expressed genes, wherein the differential expression conditions of the screened differentially expressed genes TMSB10, EIF3E and PDIA6 in the training set are respectively shown in FIGS. 1-3, the differential expression conditions of TMSB10, EIF3E and PDIA6 in the verification set are respectively shown in FIGS. 4-6, the expression conditions of TMSB10, EIF3E and PDIA6 in the endometrial cancer are respectively up-regulated, down-regulated and up-regulated, and the differences have statistical significance (P < 0.05).
Example 2 diagnostic Performance validation
1. Experimental methods
For the screened differentially expressed genes TMSB10, EIF3E and PDIA6, a receiver operating curve (ROC curve) is drawn by adopting R package 'pROC' (version 1.15.0), and the sensitivity, specificity and AUC value of the receiver operating curve are analyzed to judge the diagnostic efficacy of the receiver operating curve in a training set and a verification set when the receiver operating curve is single or combined;
when the diagnostic efficacy of the single index in the training set and the verification set is judged, the expression quantity of the gene is directly used for analysis, the level corresponding to the one point with the maximum Youden index is selected as the cutoff value of the gene, and the gene with the AUC of 0.5< AUC <0.8 is used for joint analysis;
and when the diagnosis efficiency of the index combination in the training set and the verification set is judged, Logitics regression is carried out on the expression level of each gene, the probability of whether each individual suffers from cancer is calculated through a fitted regression curve, different probability division threshold values are determined, and the sensitivity, specificity, accuracy and the like of the joint diagnosis scheme are calculated according to the determined probability division threshold values.
2. Results of the experiment
(1) ROC Curve analysis of TMSB10
The diagnostic efficacy data of TMSB10 in the training set are shown in table 1 and fig. 7, and the diagnostic efficacy data of TMSB10 in the validation set are shown in table 2 and fig. 8, which shows that TMSB10 has a certain diagnostic effect on endometrial cancer.
TABLE 1 diagnostic efficacy of TMSB10 in the training set
Gene AUC Sensitivity of the composition Specificity of
TMSB10 0.791 0.857 0.833
TABLE 2 diagnostic potency of TMSB10 in the validation set
Gene AUC Sensitivity of the composition Specificity of
TMSB10 0.772 0.814 0.657
(2) ROC Curve analysis of EIF3E
The diagnostic efficacy data of EIF3E in the training set are shown in table 3 and fig. 9, and the diagnostic efficacy data of EIF3E in the validation set are shown in table 4 and fig. 10, and the results show that EIF3E has a certain diagnostic effect on endometrial cancer.
TABLE 3 diagnostic potency of EIF3E in the training set
Gene AUC Sensitivity of the composition Specificity of
EIF3E 0.812 0.901 0.667
TABLE 4 diagnostic potency of EIF3E in validation set
Gene AUC Sensitivity of the composition Specificity of
EIF3E 0.778 0.814 0.657
(3) ROC Curve analysis of PDIA6
The diagnostic efficacy data of the PDIA6 in the training set are shown in Table 5 and FIG. 11, and the diagnostic efficacy data of the PDIA6 in the verification set are shown in Table 6 and FIG. 12, and the result shows that the PDIA6 has a certain diagnostic effect on endometrial cancer.
TABLE 5 diagnostic potency of PDIA6 in the training set
Gene AUC Sensitivity of the composition Specificity of
PDIA6 0.740 0.626 1.000
TABLE 6 diagnostic potency of PDIA6 in validation set
Gene AUC Sensitivity of the composition Specificity of
PDIA6 0.612 0.372 0.914
(4) ROC Curve analysis of TMSB10+ EIF3E + PDIA6
The diagnostic efficacy data of TMSB10+ EIF3E + PDIA6 in the training set are shown in Table 7 and FIG. 13, and the diagnostic efficacy data of TMSB10+ EIF3E + PDIA6 in the verification set are shown in Table 8 and FIG. 14, and the results show that the diagnostic effect of the combination of TMSB10+ EIF3E + PDIA6 on the endometrial cancer is obviously better than that of a single gene, so that the diagnostic efficacy is better, and the combination of the TMSB10+ EIF3E + PDIA6 can be used for diagnosing the endometrial cancer.
TABLE 7 diagnostic potency of TMSB10+ EIF3E + PDIA6 in the training set
Gene AUC Sensitivity of the composition Specificity of
TMSB10+EIF3E+PDIA6 0.959 0.945 0.833
TABLE 8 diagnostic potency of TMSB10+ EIF3E + PDIA6 in the validation set
Figure BDA0003149856720000101
Figure BDA0003149856720000111
The above description of the embodiments is only intended to illustrate the method of the invention and its core idea. It should be noted that, for those skilled in the art, without departing from the principle of the present invention, several improvements and modifications can be made to the present invention, and these improvements and modifications will also fall into the protection scope of the claims of the present invention.

Claims (10)

1. Use of a biomarker in the manufacture of a product for diagnosing or predicting early stage endometrial cancer, wherein the biomarker comprises TMSB10, EIF3E, PDIA 6;
preferably, the biomarker TMSB10 is up-regulated in endometrial cancer;
preferably, the biomarker EIF3E is down-regulated in endometrial cancer;
preferably, the biomarker PDIA6 is upregulated in endometrial cancer.
2. The use according to claim 1, wherein the product comprises a reagent for detecting the presence, absence and/or amount of the biomarkers TMSB10, EIF3E, PDIA6 or functional fragments thereof in a sample.
3. Use according to claim 2, wherein the reagents comprise reagents for detecting the presence, absence and/or amount of the biomarkers TMSB10, EIF3E, PDIA6 or functional fragments thereof in a sample using digital imaging techniques, protein immunization techniques, dye techniques, nucleic acid sequencing techniques, nucleic acid hybridization techniques, chromatography techniques, mass spectrometry techniques;
preferably, the reagents for detecting the presence, absence and/or amount of the biomarkers TMSB10, EIF3E, PDIA6 or functional fragments thereof in a sample using protein immunoassay techniques include antibodies;
more preferably, the antibody is a labeled antibody specific for an epitope of the biomarkers TMSB10, EIF3E, PDIA6 or functional fragments thereof;
preferably, the reagent for detecting the presence, absence and/or amount of the biomarkers TMSB10, EIF3E, PDIA6 or functional fragments thereof in the sample using dye technology comprises a dye;
more preferably, the dye is a dye specific for the biomarkers TMSB10, EIF3E, PDIA6 or functional fragments thereof;
preferably, the reagents for detecting the presence, absence and/or amount of the biomarkers TMSB10, EIF3E, PDIA6 or functional fragments thereof in a sample using nucleic acid sequencing technology comprise primers;
more preferably, the primer is a primer that binds to the sequence of the biomarker TMSB10, EIF3E, PDIA6, or a functional fragment thereof;
preferably, the reagents for the presence, absence and/or amount of the biomarkers TMSB10, EIF3E, PDIA6 or functional fragments thereof in a sample using nucleic acid hybridization techniques comprise probes;
more preferably, the probe is a labeled probe complementary to the sequence of the biomarkers TMSB10, EIF3E, PDIA6 or a functional fragment thereof.
4. The use of claim 2 or 3, wherein the sample comprises a body fluid, a tissue;
preferably, the bodily fluid comprises blood, plasma, serum, lymph, urine, serosal cavity fluid, spinal fluid, synovial fluid, aqueous humor, tears, saliva.
5. An article of manufacture for diagnosing or predicting early stage endometrial cancer comprising reagents for detecting the biomarkers TMSB10, EIF3E, PDIA6, or functional fragments thereof;
preferably, the product comprises a detection kit, a chip and test paper.
6. The product according to claim 5, characterized in that the detection kit comprises primers and/or probes for detecting the biomarkers TMSB10, EIF3E, PDIA6 or functional fragments thereof;
preferably, the detection kit further comprises a reagent for detecting an internal reference gene;
more preferably, the reagent for detecting the internal reference gene comprises a primer and/or a probe aiming at the internal reference gene;
preferably, the detection kit further comprises dNTPs and Mg2+Ions, DNA polymerase or DNA polymerase containing dNTPs, Mg2+Ionic, DNA polymerase PCR systems;
preferably, the detection kit further comprises a bisulfite or hydrazine salt.
7. Application of a reagent for detecting biomarkers TMSB10, EIF3E, PDIA6 or functional fragments thereof in preparation of products for diagnosing or predicting early endometrial cancer.
8. A detection system or device for diagnosing whether a subject has, or is at risk for, endometrial cancer, comprising:
(1) an analysis unit adapted to measure the amount of the biomarkers TMSB10, EIF3E, PDIA6 or functional fragments thereof in a sample of a subject;
(2) an evaluation unit comprising a stored reference and a data processor having implemented an algorithm for comparing the amount of the biomarkers TMSB10, EIF3E, PDIA6 measured by the analysis unit with the stored reference, thereby diagnosing whether endometrial cancer is present or at risk of endometrial cancer.
9. The application of the biomarkers TMSB10, EIF3E and PDIA6 in preparing a pharmaceutical composition for preventing and/or treating endometrial cancer;
preferably, the pharmaceutical composition comprises an inhibitor for inhibiting the expression level of TMSB10, a promoter for promoting the expression level of EIF3E, and an inhibitor for inhibiting the expression level of PDIA 6.
10. A method of screening for a candidate agent for preventing and/or treating endometrial cancer, said method comprising the steps of:
(1) treating a system expressing or containing TMSB10, EIF3E, PDIA6 with a test substance;
(2) detecting the expression of TMSB10, EIF3E and PDIA6 in the system;
(3) test substances which can reduce the expression level of TMSB10, increase the expression level of EIF3E and reduce the expression level of PDIA6 are selected as candidate drugs.
CN202110761222.5A 2021-07-06 2021-07-06 Biomarker for diagnosing endometrial cancer and product and application thereof Pending CN113249491A (en)

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Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110656174A (en) * 2019-09-10 2020-01-07 成都康珞生物科技有限公司 Specific marker closely related to occurrence and development of primary hepatocellular carcinoma and application thereof
CN113493839A (en) * 2021-09-06 2021-10-12 北京泱深生物信息技术有限公司 Application of gene marker combination in diagnosis of endometrial cancer
CN113493840A (en) * 2021-09-07 2021-10-12 北京泱深生物信息技术有限公司 Marker for endometrial cancer diagnosis and derivative product and application thereof
CN113736883A (en) * 2021-09-08 2021-12-03 河北医科大学第二医院 Marker molecule related to cervical cancer and detection kit
CN115184611A (en) * 2022-08-01 2022-10-14 中国医学科学院北京协和医院 Endometrial cancer stratification related marker and application thereof
CN115825414A (en) * 2023-01-09 2023-03-21 中国医学科学院北京协和医院 Blood or urine metabolic marker and application thereof in endometrial cancer early screening
CN116004815A (en) * 2022-08-02 2023-04-25 山东大学齐鲁医院 Endometrial cancer prognosis model based on copper death-related lncRNA and application thereof in immunotherapy

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108738346A (en) * 2015-09-25 2018-11-02 普罗维斯塔诊断公司 Biological marker for detecting the breast cancer in the women with fine and close mammary gland
CN111647648A (en) * 2020-05-21 2020-09-11 北斗生命科学(广州)有限公司 Gene panel for detecting breast cancer gene mutation and detection method and application thereof
CN112176065A (en) * 2020-08-20 2021-01-05 中国医学科学院北京协和医院 Reagents and methods for prognosis of cervical cancer or prediction of risk of cervical cancer recurrence or metastasis

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108738346A (en) * 2015-09-25 2018-11-02 普罗维斯塔诊断公司 Biological marker for detecting the breast cancer in the women with fine and close mammary gland
CN111647648A (en) * 2020-05-21 2020-09-11 北斗生命科学(广州)有限公司 Gene panel for detecting breast cancer gene mutation and detection method and application thereof
CN112176065A (en) * 2020-08-20 2021-01-05 中国医学科学院北京协和医院 Reagents and methods for prognosis of cervical cancer or prediction of risk of cervical cancer recurrence or metastasis

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
JINHUI LIU等: "Identification of molecular markers associated with the progression and prognosis of endometrial cancer: a bioinformatic study", 《CANCER CELL INTERNATIONAL》 *
MARÍA JOSÉ BESSO等: "Identification of early stage recurrence endometrial cancer biomarkers using bioinformatics tools", 《ONCOLOGY REPORTS》 *
ZEFANG TANG等: "GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses", 《NUCLEIC ACIDS RESEARCH》 *
张志凌: "GnRH拮抗剂cetrorelix在子宫内膜癌治疗中作用机制研究", 《中国博士学位论文全文数据库(电子期刊)》 *
杜雪莲: "基因芯片检测子宫内膜癌放射敏感性及血管生成相关基因的初步研究", 《中国博士学位论文全文数据库(电子期刊)》 *

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110656174A (en) * 2019-09-10 2020-01-07 成都康珞生物科技有限公司 Specific marker closely related to occurrence and development of primary hepatocellular carcinoma and application thereof
CN110656174B (en) * 2019-09-10 2022-09-27 成都康珞生物科技有限公司 Specific marker closely related to occurrence and development of primary hepatocellular carcinoma and application thereof
CN113493839A (en) * 2021-09-06 2021-10-12 北京泱深生物信息技术有限公司 Application of gene marker combination in diagnosis of endometrial cancer
CN113493840A (en) * 2021-09-07 2021-10-12 北京泱深生物信息技术有限公司 Marker for endometrial cancer diagnosis and derivative product and application thereof
CN113736883A (en) * 2021-09-08 2021-12-03 河北医科大学第二医院 Marker molecule related to cervical cancer and detection kit
CN115184611A (en) * 2022-08-01 2022-10-14 中国医学科学院北京协和医院 Endometrial cancer stratification related marker and application thereof
CN116004815A (en) * 2022-08-02 2023-04-25 山东大学齐鲁医院 Endometrial cancer prognosis model based on copper death-related lncRNA and application thereof in immunotherapy
CN115825414A (en) * 2023-01-09 2023-03-21 中国医学科学院北京协和医院 Blood or urine metabolic marker and application thereof in endometrial cancer early screening
CN115825414B (en) * 2023-01-09 2023-04-25 中国医学科学院北京协和医院 Blood or urine metabolic marker and application thereof in endometrial cancer early screening

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Application publication date: 20210813