CN104805197A - Method for taking molecular marker in diagnosis and prognosis evaluation of breast cancer - Google Patents
Method for taking molecular marker in diagnosis and prognosis evaluation of breast cancer Download PDFInfo
- Publication number
- CN104805197A CN104805197A CN201510165402.1A CN201510165402A CN104805197A CN 104805197 A CN104805197 A CN 104805197A CN 201510165402 A CN201510165402 A CN 201510165402A CN 104805197 A CN104805197 A CN 104805197A
- Authority
- CN
- China
- Prior art keywords
- breast cancer
- prognosis
- expression level
- type
- expression
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
- C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/118—Prognosis of disease development
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/158—Expression markers
Landscapes
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Analytical Chemistry (AREA)
- Zoology (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Physics & Mathematics (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Molecular Biology (AREA)
- Hospice & Palliative Care (AREA)
- Biophysics (AREA)
- Oncology (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Abstract
The invention relates to a method for taking the breast cancer molecular marker S100A8/A9 in diagnosis and prognosis evaluation of the breast cancer. According to the method, results show that the expression indexes of the molecular marker S100A8/A9 in breast cancer patients with different molecular pathological subtypes are different, that is, thesubtypemolecular marker S100A8/A9 is highly expressed in a substrate cellular type (basal-like) breast cancer patient and a Her-2 amplified) overexpression type breast cancer patient, but is relatively low in expression index in a lumen epithelia A type (Luminal A) breast cancer patient and a lumen epithelia B type (Luminal B) subtype breast cancer patient, that is, the statistic difference is obvious. For published NKI breast cancer chip data, patients are divided into a high group and a low group based on S100A8/A9 for Kaplan-Meier survivorship curve analysis, results show that the negative correlation between the S100A9 expression level and the total survival rate is obvious, the prognosis of a breast cancer patient with high S100A9 expression is poor, and the prognosis application value of prompting breast cancer is high.
Description
Technical field
The invention belongs to biotechnology and medical field, relate to the method for a kind of molecular marker for breast cancer diagnosis and prognosis evaluation.
Background technology
Mammary cancer is one of modal malignant tumour of women, and sickness rate accounts for the 7-10% of the various malignant tumour of whole body, occupies first of female malignant sickness rate.China's breast cancer incidence rises year by year in recent ten years, and age of onset is tending towards young, the health of serious threat China women.Mammary cancer is as high molecular different substantiality disease, the anatomy continued to use can not meet its current clinical diagnosis and treatment demand with histologic classification by stages, and especially lacking can signal tumor biological behaviour clinical treatment is provided to breast cancer tissue's credit class methods of directive function.In recent years, people attempt adopting various high-throughput molecular engineering method to be familiar with mammary cancer inward nature.Comparatively be recognized that at present and mammary cancer is divided into 4 types, i.e. epithelium (expressing normal breast epithelium hormone receptor, cytokeratin and genes involved) A type (Luminal A), epithelium Type B (Luminal B, comparatively A type hormone receptor level is low, histologic grade is high), HER-2 process LAN type and substrate template (basal-like expresses breast epithelium substrate sample or stem cell genes involved).This 4 type, in clinical studyes a large amount of afterwards, confirms that they have specificity in prognosis and therapeutic response etc.
S100A8 albumen (Calgranulin A albumen, MRP8 albumen) and S100A9 albumen (Calgranulin B albumen, MRP14 albumen) all belong to calcium binding protein S100 protein family member, both often form heterodimer S100A8/A9 albumen composition (being called for short S100A8/A9) in calcium ion dependency mode, express in the circulating cycle in property granulocyte, mononuclear macrophage.Can inflammatory reaction be participated in, regulate Growth of Cells differentiation, growth inhibition, cell death inducing etc.Research in recent years find S100A8/A9 and various diseases closely related, particularly its may act on for neoplastic disease proliferation and apoptosis.But there is no the report that it is applied to breast cancer diagnosis and prognosis at present.
Summary of the invention
The object of this invention is to provide the method for a kind of molecular marker for breast cancer diagnosis and prognosis evaluation.Described molecular marker can be used for helping mammary cancer to carry out gene type and prognosis evaluation.
Technical solutions according to the invention are:
(1) gene type mensuration is carried out to the object suffering from mammary cancer: obtain test sample from the object suffering from mammary cancer; Measure the expression level of S100A8 and S100A9 in described test sample; Analyze the dependency of expression level and mastocarcinoma gene somatotype: the expression level of S100A8 and S100A9 of mammary cancer basal cell type (basal-like) and Her-2 process LAN type (Her-2 amplified) is high, and in epithelium A type (Luminal A) and epithelium Type B (Luminal B) hypotype, expression amount is lower.
(2) prognosis evaluation being carried out to the object suffering from mammary cancer: according to mammary cancer microarray data, by dividing into groups to S100A8 and the S100A9 expression level of object, thus analyzing the dependency of expression level and Prognosis in Breast Cancer level.The object prognosis survival that the expression level of S100A9 is high is poor; The object prognosis survival that the expression level of S100A9 is low is good.
Described gene type measuring method is:
1) RNA extracts and reverse transcription
Obtain the postoperative tissue of patient with breast cancer, separating mRNA, becomes cDNA by RNA reverse transcription in the system of 20 μ L of each sample 1 μ g;
2）qRT-PCR
Using SYBR method, take cDNA as template, and amplifying target genes S100A8 and S100A9 does internal reference with β-actin gene; Reaction system is 25 μ L, and response procedures is: denaturation 95 DEG C, 10min; Circulate 95 DEG C, 15sec, 60 DEG C, 1min, totally 40 circulations; Gene relative expression quantity adopts formula 2-△ △ ct to calculate, the difference of analysis purposes gene expression amount;
Described separating mRNA, with the purification kit of Ying Jun company (Invitrogen), damping fluid group and proteolytic enzyme;
The mammary cancer microarray data delivered that what described mammary cancer microarray data adopted is in Teh Netherlands Cancer Inst (Netherlands Cancer Institute, NKI).
Advantage of the present invention is: the present invention has simple to operate, that specificity is high, susceptibility is high advantage by adopting markers for breast cancer S100A8/A9 to carry out diagnosis and prognosis assessment to mammary cancer.
Accompanying drawing explanation
Fig. 1 is the expression level of S100A8 and S100A9 of mastocarcinoma gene somatotype dissimilar in NKI display.
Fig. 2 is gene expression correlation analysis, and wherein (A) is S100A8 and ESR1(estrogen receptor alpha); (B) be S100A8 and GATA-3; (C) be S100A9 and ESR1(estrogen receptor alpha); (D) be S100A9 and GATA-3.
Fig. 3 is the Kaplan-Meier survival analysis curve after dividing into groups according to S100A8 and the S100A9 expression level of patient with breast cancer in NKI database.
Fig. 4 is qRT-PCR primer sequence.
Embodiment
Now the present invention is further illustrated in conjunction with the drawings and the specific embodiments.
As shown in the figure, concrete steps of the invention process are:
(1) gene type mensuration is carried out to the object suffering from mammary cancer: obtain test sample from the object suffering from mammary cancer; Measure the expression level of S100A8 and S100A9 in described test sample; Analyze the dependency of expression level and mastocarcinoma gene somatotype:
From Figure 1A: expression level expression level in the mammary cancer object of Her2+/basal-like somatotype of S100A8 is higher, and in the patient with breast cancer of Luminal A/B somatotype expression level lower (P<0.001).In Figure 1B, the expression level of visible S100A9 expression level in the mammary cancer object of Her2+/basal-like somatotype is higher, and in the patient with breast cancer of Luminal A/B somatotype expression level lower (P<0.001).
(2) prognosis evaluation being carried out to the object suffering from mammary cancer: according to mammary cancer microarray data, by dividing into groups to S100A8 and the S100A9 expression level of object, thus analyzing the dependency of expression level and Prognosis in Breast Cancer level; The object prognosis survival that the expression level of S100A9 is high is poor; The object prognosis survival that the expression level of S100A9 is low is good.
Concrete correlated results is:
As can be seen from Fig. 3 A, 3B: in the Kaplan-Meier survival analysis curve according to the grouping of S100A8/S100A9 expression level, S100A9 expression level and overall survival exist significant negative correlation (P<0.05); S100A8 expression level and overall survival dependency not obvious.
From Fig. 3 C, 3D: the S100A8/S100A9 expression level according to the grouping of prognosis situation all exists significant difference (P<0.001), prompting S100A8/S100A9 expression level can as the prognostic marker of mammary cancer.
Described gene type measuring method is:
1) RNA extracts and reverse transcription
Obtain the postoperative tissue of patient with breast cancer, separating mRNA, becomes cDNA by RNA reverse transcription in the system of 20 μ L of each sample 1 μ g;
2）qRT-PCR
Using SYBR method, take cDNA as template, and amplifying target genes S100A8 and S100A9 does internal reference with β-actin gene; Reaction system is 25 μ L, and ABI Stepone Plus real-time quantitative PCR instrument reacts.Response procedures is: denaturation 95 DEG C, 10min; Circulate 95 DEG C, 15sec, 60 DEG C, 1min, totally 40 circulations; Gene relative expression quantity adopts formula 2-△ △ ct to calculate, the difference of analysis purposes gene expression amount.
Described separating mRNA, with the purification kit of Ying Jun company (Invitrogen), damping fluid group and proteolytic enzyme; The mammary cancer microarray data delivered that what described mammary cancer microarray data adopted is in Teh Netherlands Cancer Inst (Netherlands Cancer Institute, NKI).
In Fig. 3 of the present invention there is remarkable negative correlation (P<0.0001) in the expression level of S100A8/S100A9 and the expression level of ESR1 and GATA-3.
Claims (4)
1. molecular marker is used for a method for breast cancer diagnosis and prognosis evaluation, it is characterized in that described method comprises:
(1) gene type mensuration is carried out to the object suffering from mammary cancer: obtain test sample from the object suffering from mammary cancer; Measure
The expression level of S100A8 and S100A9 in described test sample; The expression level analyzing expression level and the dependency mammary cancer basal cell type of mastocarcinoma gene somatotype and S100A8 and S100A9 of Her-2 process LAN type is high, and in epithelium A type (Luminal A) and epithelium Type B (Luminal B) hypotype, expression amount is lower;
(2) prognosis evaluation is carried out to the object suffering from mammary cancer: according to mammary cancer microarray data, by the S100A8 to object
Divide into groups with S100A9 expression level, thus analyze the dependency of expression level and Prognosis in Breast Cancer level: it is poor that the object prognosis that the expression level of S100A9 is high is survived; The object prognosis survival that the expression level of S100A9 is low is good.
2. molecular marker according to claim 1 is used for the method for breast cancer diagnosis and prognosis evaluation, it is characterized in that described gene type measuring method is:
(1) mRNA of patient with breast cancer's tissue extracts and reverse transcription
Obtain the postoperative tissue of patient with breast cancer, separating mRNA, becomes cDNA by RNA reverse transcription in the system of 20 μ L of each sample 1 μ g;
(2) qRT-PCR of patient with breast cancer's tissue measures
Using SYBR method, take cDNA as template, and amplifying target genes S100A8 and S100A9 does internal reference with β-actin gene; Reaction system is 25 μ L, and response procedures is: denaturation 95 DEG C, 10min; Circulate 95 DEG C, 15sec, 60 DEG C, 1min, totally 40 circulations; Gene relative expression quantity adopts formula 2-△ △ ct to calculate, the difference of analysis purposes gene expression amount.
3. molecular marker according to claim 1 is used for the method for breast cancer diagnosis and prognosis evaluation, it is characterized in that described separating mRNA, with the purification kit of Ying Jun company, damping fluid group and proteolytic enzyme.
4. molecular marker according to claim 1 is used for the method for breast cancer diagnosis and prognosis evaluation, and what it is characterized in that described mammary cancer microarray data adopts is the mammary cancer microarray data delivered of Teh Netherlands Cancer Inst.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510165402.1A CN104805197A (en) | 2015-04-09 | 2015-04-09 | Method for taking molecular marker in diagnosis and prognosis evaluation of breast cancer |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510165402.1A CN104805197A (en) | 2015-04-09 | 2015-04-09 | Method for taking molecular marker in diagnosis and prognosis evaluation of breast cancer |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104805197A true CN104805197A (en) | 2015-07-29 |
Family
ID=53690393
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510165402.1A Pending CN104805197A (en) | 2015-04-09 | 2015-04-09 | Method for taking molecular marker in diagnosis and prognosis evaluation of breast cancer |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104805197A (en) |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105483254A (en) * | 2015-12-31 | 2016-04-13 | 高勇 | Diagnostic marker for breast cancer |
| CN106319057A (en) * | 2016-08-31 | 2017-01-11 | 青岛市中心医院 | Method for early monitoring radioactive pneumonia fibrosis caused by tumor radiotherapy |
| CN108456730A (en) * | 2018-02-27 | 2018-08-28 | 海门善准生物科技有限公司 | Distant place risk of recurrence gene group and in-vitro diagnosis product and application in breast cancer parting |
| CN108949983A (en) * | 2018-07-23 | 2018-12-07 | 福州大彻精准医学科技有限公司 | Breast cancer parting gene group and its application |
| CN108977542A (en) * | 2018-07-27 | 2018-12-11 | 拓普基因科技（广州）有限责任公司 | The oligonucleotide probe group and detection method and application that monitoring breast cancer recurs in real time |
| WO2020035063A1 (en) * | 2018-08-17 | 2020-02-20 | 北京市心肺血管疾病研究所 | Application of serum s100a8/a9 complex level in the prognosis determination of acute myocardial infarction |
| CN113862363A (en) * | 2021-10-27 | 2021-12-31 | 中山大学附属第一医院 | Application of immune related gene in kit and system for breast cancer prognosis |
| CN116377048A (en) * | 2022-04-22 | 2023-07-04 | 广州市妇女儿童医疗中心 | Application of S100A8/A9 complex in diagnosis and treatment of congenital megacolon |
| CN117577176A (en) * | 2023-12-01 | 2024-02-20 | 广东省第二人民医院（广东省卫生应急医院） | Quantitative bladder cancer molecular typing method and device |
| CN117604110A (en) * | 2024-01-23 | 2024-02-27 | 杭州华得森生物技术有限公司 | Biomarker for breast cancer diagnosis and prognosis and application thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1852974A (en) * | 2003-06-09 | 2006-10-25 | 密歇根大学董事会 | Compositions and methods for treating and diagnosing cancer |
| WO2008079269A2 (en) * | 2006-12-19 | 2008-07-03 | Genego, Inc. | Novel methods for functional analysis of high-throughput experimental data and gene groups identified therfrom |
-
2015
- 2015-04-09 CN CN201510165402.1A patent/CN104805197A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1852974A (en) * | 2003-06-09 | 2006-10-25 | 密歇根大学董事会 | Compositions and methods for treating and diagnosing cancer |
| WO2008079269A2 (en) * | 2006-12-19 | 2008-07-03 | Genego, Inc. | Novel methods for functional analysis of high-throughput experimental data and gene groups identified therfrom |
Cited By (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105483254A (en) * | 2015-12-31 | 2016-04-13 | 高勇 | Diagnostic marker for breast cancer |
| CN106319057A (en) * | 2016-08-31 | 2017-01-11 | 青岛市中心医院 | Method for early monitoring radioactive pneumonia fibrosis caused by tumor radiotherapy |
| CN108456730B (en) * | 2018-02-27 | 2021-01-05 | 海门善准生物科技有限公司 | Application of recurrence risk gene group as marker in preparation of product for evaluating recurrence risk at distant place in breast cancer molecular typing |
| CN108456730A (en) * | 2018-02-27 | 2018-08-28 | 海门善准生物科技有限公司 | Distant place risk of recurrence gene group and in-vitro diagnosis product and application in breast cancer parting |
| CN108949983A (en) * | 2018-07-23 | 2018-12-07 | 福州大彻精准医学科技有限公司 | Breast cancer parting gene group and its application |
| CN108949983B (en) * | 2018-07-23 | 2022-09-30 | 福州大彻精准医学科技有限公司 | Breast cancer typing gene group and application thereof |
| CN108977542A (en) * | 2018-07-27 | 2018-12-11 | 拓普基因科技（广州）有限责任公司 | The oligonucleotide probe group and detection method and application that monitoring breast cancer recurs in real time |
| WO2020035063A1 (en) * | 2018-08-17 | 2020-02-20 | 北京市心肺血管疾病研究所 | Application of serum s100a8/a9 complex level in the prognosis determination of acute myocardial infarction |
| CN113862363A (en) * | 2021-10-27 | 2021-12-31 | 中山大学附属第一医院 | Application of immune related gene in kit and system for breast cancer prognosis |
| CN116377048A (en) * | 2022-04-22 | 2023-07-04 | 广州市妇女儿童医疗中心 | Application of S100A8/A9 complex in diagnosis and treatment of congenital megacolon |
| CN116377048B (en) * | 2022-04-22 | 2024-05-07 | 广州市妇女儿童医疗中心 | Application of S100A8/A9 complex in diagnosis and treatment of congenital megacolon |
| CN117577176A (en) * | 2023-12-01 | 2024-02-20 | 广东省第二人民医院（广东省卫生应急医院） | Quantitative bladder cancer molecular typing method and device |
| CN117604110A (en) * | 2024-01-23 | 2024-02-27 | 杭州华得森生物技术有限公司 | Biomarker for breast cancer diagnosis and prognosis and application thereof |
| CN117604110B (en) * | 2024-01-23 | 2024-04-19 | 杭州华得森生物技术有限公司 | Biomarker for breast cancer diagnosis and prognosis and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104805197A (en) | Method for taking molecular marker in diagnosis and prognosis evaluation of breast cancer | |
| Economopoulou et al. | Liquid biopsy: an emerging prognostic and predictive tool in head and neck squamous cell carcinoma (HNSCC). Focus on circulating tumor cells (CTCs) | |
| CN109890394A (en) | The Microrna of biomarker as endometriosis | |
| Jin et al. | Liquid biopsy in uveal melanoma: are we there yet? | |
| WO2013052480A1 (en) | Marker-based prognostic risk score in colon cancer | |
| AU2022204690A1 (en) | Methods For Predicting Risk Of Metastasis In Cutaneous Melanoma | |
| US20110070582A1 (en) | Gene Expression Profiling for Predicting the Response to Immunotherapy and/or the Survivability of Melanoma Subjects | |
| US20170275703A1 (en) | Treatment and detection of melanoma | |
| Song et al. | Combined detection of HER2, Ki67, and GSTP1 genes on the diagnosis and prognosis of breast cancer | |
| Fang et al. | hsa‑miR‑5580‑3p inhibits oral cancer cell viability, proliferation and migration by suppressing LAMC2 | |
| US20180258494A1 (en) | Materials and methods for bladder cancer detection | |
| Roberts et al. | Prostate-based biofluids for the detection of prostate cancer: A comparative study of the diagnostic performance of cell-sourced RNA biomarkers | |
| US20190316205A1 (en) | Mmp1 gene transcript for use as a marker for diagnosis of ovarian cancer prognosis, and test method | |
| Wei et al. | Expression of miR-4739 in gastric cancer and its relationship with clinical pathological features of patients | |
| CN108103202A (en) | 7 kind serum excretion body miRNAs relevant with liver cancer diagnosis and treatment and its application | |
| CN107937520B (en) | Molecular marker, inhibitor, kit and medicament related to colorectal cancer | |
| CN106950370A (en) | The small nucleic acid diagnosis of colorectal carcinoma molecular combinations of blood | |
| CN106939354A (en) | MiRNA 4530 as pulmonary cancer diagnosis mark application | |
| Attia et al. | Altered expression of microRNAs in the bone marrow of multiple myeloma patients and their relationship to cytogenetic aberrations | |
| RU2547583C2 (en) | Diagnostic technique for breast cancer | |
| CN109797218B (en) | Application of integrin beta 4 in preparation of reagent or medicine for distinguishing colon cancer from rectal cancer | |
| Kulasinghe et al. | Current trends and management in head and neck cancers | |
| EP2083087B1 (en) | Method for determining tongue cancer | |
| RU2823255C1 (en) | Method for prediction of recurrent thyroid cancer after radical surgery | |
| CN104774916B (en) | Biomarker combination used for detection of chemotherapy curative effect and/or prognosis of metastatic colorectal cancer and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| EXSB | Decision made by sipo to initiate substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20150729 |