CN116240285A - System and method for assessing the efficacy of chemotherapy or postoperative disease progression in cervical cancer - Google Patents
System and method for assessing the efficacy of chemotherapy or postoperative disease progression in cervical cancer Download PDFInfo
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Abstract
The invention discloses a system and a method for evaluating the chemo-treatment effect of cervical cancer or the disease progress after operation, wherein the system comprises a total concentration of blood plasma cell-free DNA, a purity detection module, an analysis module and a classification module; the invention adopts the total concentration of the plasma cell-free DNA as an index of cervical cancer chemotherapy sensitivity or postoperative disease progress, summarizes and obtains a chemotherapy sensitivity and postoperative disease progress evaluation system, facilitates clinical evaluation of whether cervical cancer patients to be detected are sensitive to platinum new auxiliary chemotherapy or not, evaluates postoperative disease progress of the patients, and has important significance for guiding clinical individual medication and improving prognosis of the patients.
Description
Technical Field
The invention relates to the fields of medical technology and biological detection, in particular to a system and a method for evaluating the chemo-therapeutic effect of cervical cancer or the disease progression after operation.
Background
Cervical cancer is a common malignancy in the female reproductive system, and the best prevention and control strategy at present is early screening and vaccination. The treatment of cervical cancer is mainly performed by operation and synchronous radiotherapy and chemotherapy, and long-term complications are caused by damage to pelvic organs caused by radiotherapy, such as climacteric symptoms caused by damage to ovarian functions, and the quality of life of patients is affected, so research on cervical cancer treatment in recent years is focused on aspects of new auxiliary chemotherapy, postoperative chemotherapy and the like. The novel auxiliary chemotherapy is also called preoperative chemotherapy, and has the advantages of reducing local tumor or reducing tumor stage, facilitating the operation, eliminating difficult-to-detect micro metastasis and reducing postoperative recurrence risk.
A large amount of clinical data show that no matter the novel auxiliary chemotherapy or the postoperative chemotherapy is adopted, only part of patients react to the chemotherapy drugs, but the biomarker for effectively predicting the cervical cancer chemotherapy effect still lacks at present, and the existing imaging and tumor markers used as the evaluation method of the chemotherapy effect have some non-negligible disadvantages, such as the delay effect of imaging, low specificity of the tumor markers, no obvious change of part of patients and the like. Studies have shown that paclitaxel weekly therapy shortens the time interval for tumor regrowth compared to traditional three-week therapies, improving patient prognosis, but this result is still controversial due to the heterogeneity of the inter-patient chemotherapy effects. Therefore, there is an urgent need to develop new markers for predicting or early assessing patient chemotherapy sensitivity, thereby promoting improvement of treatment schemes, which has important significance for patient implementation of personalized treatment, patient prognosis improvement, and medical resource saving.
Surgery is the most important treatment means for early cervical cancer patients, but also brings risks to the disseminated planting of tumors in the pelvis, which is also a main cause of early recurrent death of partial patients after surgery, evaluates the postoperative disease progression of the patients, and is important for guiding postoperative adjuvant therapy. At present, the factors for evaluating the postoperative medium and high risk of cervical cancer patients are mainly based on postoperative pathological results, the effect of invasive operation of surgery in disease progression is ignored, and corresponding evaluation indexes are lacking, so that the biomarker for excavating postoperative disease progression of patients is helpful for perfecting postoperative adjuvant therapy.
The development of the field of liquid biopsy holds promise for continuously monitoring characteristic changes of tumors, and plasma free DNA (cell-free DNA) is free extracellular DNA in plasma, which is mainly derived from apoptosis of normal cells of the hematopoietic system in a healthy state and has a low content. In the course of a particular pathology or disease progression, the tissue origin composition of the cell-free DNA changes, reflecting the disease state of the patient, and an increase in the cell-free DNA concentration during treatment may reflect the therapeutic effect of the patient, which is expected to be a new biomarker for the assessment of disease progression after cervical cancer surgery.
Disclosure of Invention
The invention aims at overcoming the defects of the existing marker deficiency and chemotherapy effect evaluation method for evaluating the postoperative disease progress of cervical cancer, and provides a system and a method for evaluating the chemotherapy effect or the postoperative disease progress of cervical cancer.
In order to achieve the above purpose, the present invention is designed with the following technical scheme:
the invention provides a system for evaluating the chemo-treatment effect of cervical cancer or the postoperative disease progress, which comprises a purity detection module of blood plasma cell-free DNA, a concentration detection module of blood plasma cell-free DNA and a classification module; wherein,,
(1) Purity detection module of plasma cell-free DNA: the method is used for analyzing the purity of the cell-free DNA in the blood plasma, extracting the cell-free DNA in the blood plasma, and detecting the purity of the cell-free DNA in the blood plasma through Fragment Analyzer;
(2) Concentration detection module of plasma cell-free DNA: the method is used for counting the concentration of the cell-free DNA in the blood plasma, carrying out quantitative analysis after the extraction of the cell-free DNA in the blood plasma, and counting the concentration of the cell-free DNA in the blood plasma.
(3) And a classification module: the method is used for evaluating the chemotherapy effect of the patient or judging whether the patient is in postoperative disease progress, analyzing the ratio of cell-free DNA concentration before and after chemotherapy, and evaluating the chemotherapy effect of the patient; alternatively, the post-operative cell-free DNA concentration is analyzed to assess whether the patient is in post-operative disease progression.
Further, in the purity detection module of the plasma cell-free DNA, the quality standard of the plasma cell-free DNA is as follows:
cell-free DNA in plasma showed a distinct peak at 166bp, indicating no distinct nuclear genomic contamination.
Further, in the concentration detection module of the cell-free DNA in the blood plasma, the concentration data is the concentration of the cell-free DNA in the blood plasma, and the unit is ng/mL.
Still further, in the classifying module,
a. patient chemotherapy effects were assessed based on changes in cell-free DNA concentration before and after treatment:
if the ratio of the cell-free DNA concentration of the plasma after 1 day of chemotherapy to the cell-free DNA concentration of the plasma before chemotherapy is more than 2, the chemotherapy effect of the patient is considered to be poor, otherwise, the chemotherapy effect of the patient is good;
b. assessing whether the patient is in post-operative disease progression based on the post-operative cell-free DNA concentration magnitude:
if the post-operation plasma cell-free DNA concentration is increased to more than 30ng/mL, otherwise, the blood plasma cell-free DNA concentration is not;
the invention also provides a method for analyzing and detecting by using the cervical cancer chemotherapy effect or the postoperative disease progression detection system, which comprises the following steps:
1) Sample separation and cell-free DNA extraction: collecting whole blood samples of a person to be detected before and after chemotherapy, separating plasma, and then extracting plasma cell-free DNA (namely, the plasma cell-free DNA) (a plasma cell-free DNA extraction kit The QIAamp ccfDNA/RNAkit, product number 55184);
2) Sample quality inspection: detecting the purity of the plasma cell-free DNA by Fragment Analyzer;
3) Plasma cell-free DNA quantification: 1ul of each cell-free DNA sample was taken and the concentration of plasma cell-free DNA was quantitatively determined by Qubit,
4) Application analysis in assessing chemotherapy effects or post-operative disease progression:
a. patient chemotherapy effects were assessed based on the ratio of cell-free DNA concentration before and after chemotherapy:
if the ratio of the cell-free DNA concentration of the plasma after 1 day of chemotherapy to the cell-free DNA concentration of the plasma before chemotherapy is more than 2, the chemotherapy effect of the patient is considered to be poor, otherwise, the chemotherapy effect of the patient is good;
b. assessing whether the patient is in post-operative disease progression based on the magnitude of the post-operative cell-free DNA concentration value:
if the concentration of the cell-free DNA in the plasma after the treatment is increased to be more than 30ng/mL, the patient is considered to belong to the recurrent high risk group, otherwise, the patient does not belong to the recurrent high risk group;
further, in the step 1), the plasma separation step is as follows: the plasma and blood cells were separated by centrifugation at 2000g for 10 minutes in a low temperature centrifuge at 4℃and the upper plasma was subjected to a secondary centrifugation and centrifuged at 3000g for 15 minutes in a low temperature centrifuge at 4 ℃.
Still further, in the step 2), fragment Analyzer detected plasma cell-free DNA shows a significant peak at 166bp, and no significant nuclear genome contamination considers the sample quality to be satisfactory
The invention also provides application of the system in assessing the chemo-therapeutic effect of cervical cancer or the postoperative disease progression.
The invention also provides application of the method in assessing the chemo-therapeutic effect of cervical cancer or the disease progression after operation.
The biological information analysis method and the biological information analysis system can carry out batch analysis on a plurality of samples.
The invention has the beneficial effects that:
the invention discovers that the change of the concentration of the cell-free DNA in the blood plasma is closely related to the chemotherapy reaction for the first time, and the rise of the concentration of the cell-free DNA in the blood plasma after operation indicates the disease progress after operation. Therefore, the invention adopts the plasma cell-free DNA concentration as an evaluation index of the cervical cancer chemosensitivity, and summarizes and obtains a chemosensitivity evaluation system, which is convenient for clinical evaluation of whether cervical cancer patients to be detected are sensitive to platinum new auxiliary chemotherapeutics.
Drawings
FIG. 1 is a graph showing the relationship between the ratio of the concentration of cell-free DNA in plasma and the effect of chemotherapy one day after chemotherapy and before chemotherapy for cervical cancer patients;
in the figure, A is a corresponding relation diagram of the ratio of the neoadjuvant chemotherapy effect of 16 cervical cancer patients to the concentration of the cell-free DNA in the blood plasma and the clinical characteristics of the cervical cancer patients;
b is a ROC curve graph for distinguishing good chemotherapy effect and poor chemotherapy response by using the ratio of cell-free DNA concentration;
FIG. 2 is a graph showing the change of cell-free DNA concentration before and after operation for cervical cancer patients;
in the figure, A is a histogram of the change of cell-free DNA concentration before and after the operation of 18 cervical cancer patients;
b is a graph of the change of the plasma cfDNA concentration value before and after operation of 2 patients with bad prognosis and clinical outcome.
Detailed Description
The present invention is described in further detail below in conjunction with specific embodiments for understanding by those skilled in the art.
Example 1
The system for evaluating the chemo-treatment effect of cervical cancer or the postoperative disease progression based on the concentration ratio of the plasma cell-free DNA comprises a purity detection module of the plasma cell-free DNA, a concentration detection module of the plasma cell-free DNA and a classification module; wherein,,
(1) Purity detection module of plasma cell-free DNA: the method is used for analyzing the purity of the cell-free DNA in the blood plasma, extracting the cell-free DNA in the blood plasma, and detecting the purity of the cell-free DNA in the blood plasma through Fragment Analyzer;
(2) Concentration detection module of plasma cell-free DNA: the method is used for counting the concentration of the cell-free DNA in the blood plasma, carrying out quantitative analysis after the extraction of the cell-free DNA in the blood plasma, and counting the concentration of the cell-free DNA in the blood plasma.
(3) And a classification module: the method is used for evaluating the chemotherapy effect of the patient or judging whether the patient is in postoperative disease progress, analyzing the ratio of cell-free DNA concentration before and after chemotherapy, and evaluating the chemotherapy effect of the patient; alternatively, the post-operative cell-free DNA concentration is analyzed to assess whether the patient is in post-operative disease progression.
The method for analyzing and detecting by using the cervical cancer chemotherapy effect or postoperative disease progression detection system comprises the following steps:
1) Sample separation and cell-free DNA extraction: collecting whole blood samples of a person to be detected before and after chemotherapy, separating plasma, and then extracting plasma cell-free DNA (namely, the plasma cell-free DNA) (a plasma cell-free DNA extraction Kit The QIAamp ccfDNA/RNA Kit, product number 55184);
2) Sample quality inspection: the purity of the plasma cell-free DNA is detected by Fragment Analyzer, fragment Analyzer detects that the plasma cell-free DNA shows obvious peak at 166bp, and no obvious nuclear genome pollution considers that the quality of the sample meets the requirement;
3) Plasma cell-free DNA quantification: 1ul of each cell-free DNA sample was taken and the concentration of plasma cell-free DNA was quantitatively determined by Qubit,
4) Application analysis in assessing chemotherapy effects or post-operative disease progression:
a. patient chemotherapy effects were assessed based on the ratio of cell-free DNA concentration before and after chemotherapy:
if the ratio of the cell-free DNA concentration of the plasma after 1 day of chemotherapy to the cell-free DNA concentration of the plasma before chemotherapy is more than 2, the chemotherapy effect of the patient is considered to be poor, otherwise, the chemotherapy effect of the patient is good;
b. assessing whether the patient is in post-operative disease progression based on the magnitude of the post-operative cell-free DNA concentration value:
if the concentration of the cell-free DNA in the plasma after the treatment is increased to be more than 30ng/mL, the patient is considered to belong to the recurrent high risk group, otherwise, the patient does not belong to the recurrent high risk group;
example 2 analysis of correlation of concentration changes in cell-free DNA sheets in peripheral blood plasma of cervical cancer patients with chemotherapeutic Effect
Based on the peripheral blood plasma of 16 cervical cancer patients subjected to neoadjuvant chemotherapy before and after treatment, the system and the method are adopted to extract free DNA samples of the patient plasma, detect the purity and quantitatively analyze, and monitor the change of the cell-free DNA concentration. The relationship between the change of the cell-free DNA concentration and the treatment effect in the treatment process is analyzed, the cell-free DNA concentration of the people with poor chemotherapy effect is found to be obviously increased in one day after the treatment, and the cell-free DNA concentration ratio of the people with good chemotherapy effect and the people with poor chemotherapy effect in one day after the treatment is obviously different (P < 0.01), ROC=0.9167, so that the system and the method can be used for early evaluation of the chemotherapy effect of patients. The method comprises the following specific steps:
step 1: sample collection and transportation. Blood samples are taken from the patient before and after the patient receives treatment. Collecting 5mL of whole blood by using an EDTA anticoagulation tube, performing subsequent centrifugation at room temperature for 4 hours, centrifuging 2000g of the collected whole blood in a low-temperature centrifuge at 4 ℃ for 10 minutes, and separating plasma and blood cells; carefully transferring the upper plasma layer into a new centrifuge tube, taking care not to touch the middle buffy coat (containing white blood cells and platelets), respectively storing the buffy coat and the blood cells in a centrifuge tube of 1.5ml, and freezing in a refrigerator of-80 ℃ for later use; the upper plasma was subjected to secondary centrifugation at 3000g in a low temperature centrifuge for 15 minutes, after which the supernatant was carefully transferred to another centrifuge tube and stored in a-80 ℃ freezer for use.
Step 2: extracting and quantifying cell-free DNA of plasma. Plasma cell-free DNA was extracted using a plasma cell-free DNA extraction Kit (The QIAamp ccfDNA/RNA Kit, cat No. 55184), 1ul of each cell-free DNA sample was taken and the concentration of plasma cell-free DNA was quantitatively measured by Qubit, and the plasma cell-free DNA concentration (ng/mL) of each sample was calculated.
Step 3: correlation analysis of cell-free DNA concentration and effect of chemotherapy.
By carrying out combined analysis on the reduction ratio of the imaging tumor diameter and the change of the plasma cell-free DNA concentration in the treatment process at 3-5 weeks after primary chemotherapy, the difference of the plasma cell-free DNA concentration change of patients with the tumor diameter reduced by more than 35% after treatment is found, the tumor diameter reduced by 35% or more after chemotherapy is considered to be good in chemotherapy effect, otherwise, the chemotherapy effect is poor, the ratio (P < 0.01) of the plasma cell-free DNA concentration (cell-free DNA 2) of the patient with the good chemotherapy effect to the plasma cell-free DNA concentration (cell-free DNA 1) of the patient with the poor chemotherapy effect is obviously different (P < 0.01) in the plasma cell-free DNA concentration (cell-free DNA 2/cell-free DNA 1) of the patient after treatment.
As shown in fig. 1: the ratio of plasma cfDNA concentration one day after chemotherapy to pre-chemotherapy was significantly different in patients with good and poor chemotherapy effects (fig. 1A); ratio of cell-free DNA concentration distinguishes ROC curves with good and poor chemotherapy response, auc=0.9167 (fig. 1B); after the novel auxiliary chemotherapy, the diameters of the cfDNA2/cfDNA1 of cervical cancer patients with the tumor diameter reduced by 35% and above are respectively 0.60, 0.73, 0.75, 1.17, 1.31, 1.34, 1.57 and 2.95, the diameters of the cfDNA2/cfDNA1 of cervical cancer patients with the tumor diameter reduced by less than 35% are respectively 1.30, 2.93, 4.69, 8.16, 3.80 and 3.33, and the two groups of patients have obvious differences (P=0.0044) in the cfDNA2/cfDNA1 ratio distribution, and the area under the ROC curve with good chemotherapy effect and poor chemotherapy response can be up to 0.9167 according to the cell-free DNA concentration ratio, so that the novel auxiliary chemotherapy can be used for distinguishing the chemotherapy effect.
Example 3 clinical retrospective study protocol of post-operative peripheral blood plasma cell-free DNA sheet concentration changes in cervical cancer patients and postoperative disease progression
Based on the peripheral blood plasma of 18 cervical cancer patients before and after the operation, the system and the method are adopted to extract the free DNA sample of the patient plasma, detect the purity and quantitatively analyze, and monitor the change of the cell-free DNA concentration before and after the operation. Analyzing the relationship between the change of the cell-free DNA concentration and the clinical bad ending (recurrence, metastasis or death) of the patients in the treatment process, wherein the cell-free DNA concentration is increased after 3 cases of operations, 2 cases of patients with more than 30ng/mL have early recurrence and death (2/3), and the rest 15 cases of patients with the cell-free DNA concentration less than or equal to 30ng/mL do not have bad ending (0/15), and suggesting that the system and the method can be used for evaluating the disease progression after the operations. The method comprises the following specific steps:
step 1: sample collection and transportation. Blood samples are taken from the patient before and after the patient receives treatment. Collecting 5mL of whole blood by using an EDTA anticoagulation tube, performing subsequent centrifugation at room temperature for 4 hours, centrifuging 2000g of the collected whole blood in a low-temperature centrifuge at 4 ℃ for 10 minutes, and separating plasma and blood cells; carefully transferring the upper plasma layer into a new centrifuge tube, taking care not to touch the middle buffy coat (containing white blood cells and platelets), respectively storing the buffy coat and the blood cells in a centrifuge tube of 1.5ml, and freezing in a refrigerator of-80 ℃ for later use; the upper plasma was subjected to secondary centrifugation at 3000g in a low temperature centrifuge for 15 minutes, after which the supernatant was carefully transferred to another centrifuge tube and stored in a-80 ℃ freezer for use.
Step 2: extracting cell-free DNA from blood plasma, detecting purity and quantitatively analyzing. Plasma cell-free DNA was extracted using a plasma free nucleic acid extraction Kit (The QIAamp ccfDNA/RNA Kit, cat No. 55184), and 1ul of each cell-free DNA sample was taken and the concentration of plasma cell-free DNA was quantitatively measured by Qubit, and the plasma cell-free DNA concentration (ng/mL) of each sample was calculated.
Step 3: and (5) performing correlation analysis on the post-operation blood plasma cell-free DNA concentration and cervical cancer clinical outcome.
The clinical outcome of the patients was followed, with an increase in cell-free DNA concentration after 3 cases of surgery, with a poor prognosis (2/3) in 2 out of more than 30ng/mL patients, and no recurrence and death (0/15) in the remaining 15 cases of post-surgery cell-free DNA concentration of 30ng/mL patients, suggesting that the system and method may be used to assess post-operative disease progression.
As shown in fig. 2: in 3 cases of post-operative elevation of cell-free DNA concentration, poor prognosis (2/3) occurred in 2 out of more than 30ng/mL patients, while none of the remaining 15 cases of post-operative patients had recurrence and death (0/15) occurred in the cell-free DNA concentration of 30ng/mL or less.
Other parts not described in detail are prior art. Although the foregoing embodiments have been described in some, but not all, embodiments of the invention, it should be understood that other embodiments may be devised in accordance with the present embodiments without departing from the spirit and scope of the invention.
Claims (9)
1. A system for assessing the efficacy of chemotherapy or the progression of a postoperative condition of cervical cancer, characterized by: the system comprises a purity detection module of the plasma cell-free DNA, a concentration detection module of the plasma cell-free DNA and a classification module; wherein,,
(1) Purity detection module of plasma cell-free DNA: the method is used for analyzing the purity of the cell-free DNA in the blood plasma, extracting the cell-free DNA in the blood plasma, and detecting the purity of the cell-free DNA in the blood plasma through Fragment Analyzer;
(2) Concentration detection module of plasma cell-free DNA: the method is used for counting the concentration of the cell-free DNA in the blood plasma, carrying out quantitative analysis after extracting the cell-free DNA in the blood plasma, and counting the concentration of the cell-free DNA in the blood plasma;
(3) And a classification module: the method is used for evaluating the chemotherapy effect of the patient or judging whether the patient is in postoperative disease progress, analyzing the ratio of cell-free DNA concentration before and after chemotherapy, and evaluating the chemotherapy effect of the patient;
alternatively, the post-operative cell-free DNA concentration is analyzed to assess whether the patient is in post-operative disease progression.
2. The system for assessing the efficacy of chemotherapy or post-operative disease progression in cervical cancer according to claim 1, wherein: in the purity detection module of the plasma cell-free DNA, the quality standard of the cell-free DNA in the plasma is as follows: cell-free DNA in plasma showed a distinct peak at 166bp, indicating no distinct nuclear genomic contamination.
3. The system for assessing the efficacy of chemotherapy or post-operative disease progression in cervical cancer according to claim 1, wherein: in the concentration detection module of the plasma cell-free DNA, the concentration data is the concentration of the cell-free DNA in the plasma.
4. The system for assessing the efficacy of chemotherapy or post-operative disease progression in cervical cancer according to claim 1, wherein: in the above-mentioned classification module, the classification module,
a. patient chemotherapy effects were assessed based on changes in cell-free DNA concentration before and after treatment:
if the ratio of the cell-free DNA concentration of the plasma after 1 day of chemotherapy to the cell-free DNA concentration of the plasma before chemotherapy is more than 2, the chemotherapy effect of the patient is considered to be poor, otherwise, the chemotherapy effect of the patient is good;
b. assessing whether the patient is in post-operative disease progression based on the post-operative cell-free DNA concentration magnitude:
if the post-operative plasma cell-free DNA concentration increases beyond 30ng/mL, the other way around.
5. A method for analytical testing using the system for assessing the efficacy of chemotherapy or post-operative disease progression of cervical cancer according to claim 1, characterized in that: the method comprises the following steps:
1) Sample separation and cell-free DNA extraction: collecting whole blood samples of a person to be detected before and after chemotherapy, separating plasma, and extracting cell-free DNA of the plasma;
2) Sample quality inspection: detecting the purity and quality of the plasma cell-free DNA by Fragment Analyzer;
3) Plasma cell-free DNA quantification: 1ul of each cell-free DNA sample was taken and the concentration of plasma cell-free DNA was quantitatively determined by Qubit,
4) Application analysis in assessing chemotherapy effects or post-operative disease progression:
a. patient chemotherapy effects were assessed based on the ratio of cell-free DNA concentration before and after chemotherapy:
if the ratio of the cell-free DNA concentration of the plasma after 1 day of chemotherapy to the cell-free DNA concentration of the plasma before chemotherapy is more than 2, the chemotherapy effect of the patient is considered to be poor, otherwise, the chemotherapy effect of the patient is good;
b. assessing whether the patient is in post-operative disease progression based on the magnitude of the post-operative cell-free DNA concentration value:
if the concentration of the cell-free DNA in the plasma after treatment is increased to be more than 30ng/mL, the patient is considered to belong to the recurrent high risk group, otherwise, the patient is not.
6. The method according to claim 5, wherein: in the step 1), the plasma separation step is as follows: the plasma and blood cells were separated by centrifugation at 2000g for 10 minutes in a low temperature centrifuge at 4℃and the upper plasma was subjected to a secondary centrifugation and centrifuged at 3000g for 15 minutes in a low temperature centrifuge at 4 ℃.
7. The method according to claim 5, wherein: in the step 2), fragment Analyzer detection of the plasma cell-free DNA shows an obvious peak at 166bp, and no obvious nuclear genome pollution considers that the sample quality meets the requirement.
8. Use of the system of claim 1 for assessing the efficacy of chemotherapy or the progression of a postoperative disease in cervical cancer.
9. Use of the method of claim 5 for assessing the efficacy of chemotherapy or the progression of a postoperative disease in cervical cancer.
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| CN202311669634.1A CN117867109A (en) | 2022-12-15 | 2023-12-07 | System and method for assessing the efficacy of chemotherapy or postoperative disease progression in cervical cancer |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2353928C1 (en) * | 2007-10-11 | 2009-04-27 | Федеральное государственное учреждение "Ростовский научно-исследовательский онкологический институт" Росмедтехнологий" | Recurrent and metastasing cervical carcinoma treatment effectiveness prediction method |
| CN104720804A (en) * | 2015-04-09 | 2015-06-24 | 哈尔滨医科大学 | Method for predicting sensitivity of cervical cancer patient subjected to paclitaxel and cis-platinum adopted chemotherapy |
| US20180135138A1 (en) * | 2015-07-17 | 2018-05-17 | Toppan Printing Co., Ltd. | Method for evaluating health condition and method for predicting long-term efficacy of anticancer agent |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2353928C1 (en) * | 2007-10-11 | 2009-04-27 | Федеральное государственное учреждение "Ростовский научно-исследовательский онкологический институт" Росмедтехнологий" | Recurrent and metastasing cervical carcinoma treatment effectiveness prediction method |
| CN104720804A (en) * | 2015-04-09 | 2015-06-24 | 哈尔滨医科大学 | Method for predicting sensitivity of cervical cancer patient subjected to paclitaxel and cis-platinum adopted chemotherapy |
| US20180135138A1 (en) * | 2015-07-17 | 2018-05-17 | Toppan Printing Co., Ltd. | Method for evaluating health condition and method for predicting long-term efficacy of anticancer agent |
Non-Patent Citations (2)
| Title |
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| 万妮娅;: "血清cf-DNA定量检测对宫颈癌早期辅助诊断及预后判断中的价值", 中南医学科学杂志, no. 04, pages 35 - 37 * |
| 周冠楠;丁景新;: "液体活检在宫颈癌中的研究和应用进展", 现代妇产科进展, no. 07, pages 78 - 91 * |
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