CN103310129A - Evidence-based method for screening gastric cancer prognosis molecular markers - Google Patents
Evidence-based method for screening gastric cancer prognosis molecular markers Download PDFInfo
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Abstract
The invention discloses an evidence-based method for screening gastric cancer prognosis molecular markers. The method comprises the steps as follows: 1), an inclusion criterion is set for a gastric cancer prognosis biomarker experimental research; 2), a research evidence retrieval strategy is set; 3), the prognosis biomarkers are screened preliminarily; 4), research data are extracted; 5), quality assessment on the experimental research quality is performed; 6), standardized data are processed; 7), the prognosis biomarkers are screened; and 8), according to the screening criterion, the gastric cancer prognosis biomarkers having potential application values are screened, and the prognosis values are described. In conclusion, the evidence-based method for screening the gastric cancer prognosis biomarkers is provided, and the gastric cancer prognosis biomarkers are screened, so that the screening cost is reduced, the screening time is shortened, professional thresholds are reduced, and the application values of the prognosis biomarkers are increased.
Description
Technical field
The invention belongs to biological technical field, relate to a kind of screening technique of evidential cancer of the stomach prognosis biomarker.
Background technology
Cancer of the stomach is one of modal alimentary system malignant tumour, all occupies the malignant tumour prostatitis at China and the global incidence of disease and mortality ratio.According to the statistics of GLOBOCAN, 2008, the newly-increased morbidity of global cancer of the stomach 98.9 ten thousand examples, China is 46.3 ten thousand examples, accounts for 46.8%.Gastric cancer mortality is only second to lung cancer and occupies second, annual death toll approximately 73.7 ten thousand, and China is 35.2 ten thousand, accounts for 47.8%.China, gastric cancer mortality is number three in malignant tumour, is only second to lung cancer and liver cancer, mortality ratio is 24.71/10 ten thousand, account for all because of 18.3% of cancer mortality number, wherein deaths in men rate (32.46/10 ten thousand) is apparently higher than women (16.59/10 ten thousand), and the rural area is higher than the city.In recent years, the M ﹠ M of cancer of the stomach has slight decline, yet, gradually rejuvenation of the morbidity of cancer of the stomach, the ratio that Chinese Youth's people's cancer of the stomach accounts for whole cancer of the stomach sums rises to 3.3% by 1.7%.
In recent years, development along with the diagnosing gastric cancer technology, the Study of Etiology of cancer of the stomach and the complex treatment take excision, radiation therapy, chemicals and targeted drug treatment as the master have obtained certain progress, total life span of early carcinoma of stomach significantly improves, if can find pathology when the cancer of the stomach pathology only limits to mucous layer, the survival rate in 5 years can reach 95%.But patients with gastric cancer early stage normal lack special clinical symptoms and sign, the diagnosis of China's early carcinoma of stomach is less than 10%, causes 5 years survival rates 20%～50%.Many factors are relevant with the prognosis of cancer of the stomach, such as happening part, histological grade, lymphatic metastasis and the vascular invasion etc. of tumour.Judge at present the method for cancer of the stomach prognosis, the main by stages method of traditional metastases in local lymph node and TNM that still relies on, but the many problems in clinical can't solve by traditional method of prognosis, and such as identical TNM by stages and accept the patients with gastric cancer of identical treatment, its prognosis often has very large difference.The relation of individuation difference and prognosis and curative effect more and more is subject to clinician and researcher's attention.Therefore, what the needs searching was new can reach the susceptibility to different treatments in order to predict more accurately the patients with gastric cancer prognosis from the prognostic indicator that the TNM analysis combines, guiding clinical treatment, the final individualized treatment of realizing the patient, can improve curative effect, avoid over-treatment and reduce patient economy burden, reduce the waste of medical resource.
Biomarker is a kind of particular molecule feature that has, and is present in the biochemical molecule that can be used for weighing progression of disease and result for the treatment of in blood, body fluid or the tissue, also can be called molecular labeling.Type according to molecule can be divided into dna marker, RNA mark, protein labeling etc.; Can be divided into diagnostic flag, examination mark, prognostic markers, susceptible mark etc. according to clinical practice.Biomarker is a lot of in the application of biomedical sector, such as the evaluation of the selection of the prognosis evaluation of the diagnosis of the examination of the susceptible analysis of disease, disease, disease, disease, methods for the treatment of, result for the treatment of and drug design etc.Along with the biomarker progress of research, the biomarker of human body self is expected to become the basis of diagnosis and treatment, and helps to realize disease early diagnosis and patient's personalized treatment.
The progress of gastric cancer invasion and transfer of molecules Mechanism Study has disclosed different kinds of molecules and has changed relevant with the prognosis of cancer of the stomach.Follow the widespread use of high flux Protocols in Molecular Biology, the develop rapidly of pharmacogenomics and oncomolecularbiology research, human to cancer of the stomach from gene, mRNA and protein level to body inside and outside test carried out systematic research.The transfer of tumour is the multi-step process, comprises that oncocyte comes off, local infiltration, migration, vessel invasion and Angiogenesis, migrates to peripheral blood and survival in blood circulation, endothelial cell adhere to, ooze out blood vessel, settle down and regrow etc. in different organs.Several genes participates in the transfer regulation and control of tumour, and such as cyclin, cell adhesion molecule, proteinase, Angiogenesis and growth factor etc., and these metastasis related genes, mRNA and protein expression can be used as the prognosis biomarker of cancer of the stomach.In addition, increasing evidence demonstration, the relevant molecule of antineoplastic mechanism is identification patient individual difference's important molecular markers thing, mainly comprises three classes: 1) the effect molecular marked compound of antineoplastic, such as HER2 and EGFR; 2) the relevant molecular marked compound of antineoplastic metabolism is such as gene pleiomorphisms such as UGT1A1 and CYP2D6; 3) the related molecular marker thing of antineoplastic effect path is such as KRAS gene mutation and ERCC1 mrna expression.
Seek and find that valuable cancer of the stomach prognosis biomarker has become an important focus of present cancer of the stomach research.China attaches great importance to the research of biomarker, has listed them in 12 planning items such as state key such as grade.The researchist is devoted to find reliable cancer of the stomach relevant biomarkers always, and existing more than 20,000 researchs are published on the internal authority magazine, number are arranged with the achievement in research of thousand notes every year, and present accelerated growth trend.Wherein, the research of cancer of the stomach prognosis biomarker is particularly outstanding, and existing up to ten thousand correlative study achievements are delivered, and approximately occupies the cancer of the stomach biomarker research of half, has found up to a hundred potential prognostic markers things.
Although the researchist has carried out a large amount of clinical trials every year, spent a large amount of research manpower and financial resources.Yet the achievement in research of cancer of the stomach prognosis biomarker seldom can be applied to clinical by doctor and enterprise.Its main cause be the information of a large amount of scientific researches without rational deep processing, its value is very low.To same problem, different laboratory, the whole world may be launched research simultaneously, the object that is put to the test, sample size, and the restriction of the factors such as area, experimental design may draw the conclusion of inconsistent or even contradiction.In single research, the researchist usually can carry out expansiveness publicity to certain prognosis biomarker, and the research that comprises positive result also easy studied personnel quote.Because more than, clinician and the needed knowledge accumulation of enterprise's applying biological label and time cost will be huge, affect greatly research and the application process of cancer of the stomach prognosis biomarker.How in the biomarker data of present magnanimity, excavate and gather information, assessment and deal with data, filtering out the prognosis biomarker with using value or potential using value has become a urgent problem.
Summary of the invention
The technical problem to be solved in the present invention provides a kind of evidential cancer of the stomach prognostic markers thing screening technique, namely be a kind of excavation and information search of passing through the biomarker data of magnanimity, Scientific evaluation, processing, arrangement and deal with data filter out the method for cancer of the stomach prognosis biomarker according to evaluation criterion.
In order to solve the problems of the technologies described above, the invention provides a kind of evidential cancer of the stomach prognosis molecule label screening technique, comprise following content:
1), be the experimental study formulation inclusive criteria of cancer of the stomach prognosis biomarker:
Mainly limit at aspects such as research and design, study population, clinical effect index, biomarker species;
2), formulate research evidence search strategy:
Retrieve the Clinical Evidence database comprehensively and systematically, comprise PubMed, Embase, CBMdisc (CBM), incomparably database and the total storehouse of Chinese knowledge resource (CNKI);
Only retrieval is with the research of artificial research object, and research type and publication language are unrestricted; The list of references of research is included in retrieval in;
3), preliminary screening prognosis biomarker:
The research evidence that retrieves according to inclusive criteria, is determined kind and the quantity of cancer of the stomach prognosis biomarker, make up the biomarker database;
Biomarker screens according to the quantity of research and design method, research and the sample size of research, and filter out the biomarker that satisfies a following arbitrary condition: (1) has randomised controlled trials; (2) research quantity 〉=3 and research sample size 〉=500;
The biomarker that screens is carried out the expansion of evidence and search for again, enrich clinical evidence;
4), research data extracts:
Independently carry out data by 2 researchers according to the research data extraction content that pre-establishes and standard and extract and cross check, guarantee that research data extracts and the result of quality assessment has consistance, transfer to the 3rd researcher when at sixes and sevens and determine;
If used identical research object, choose the research sample size maximum or that comprise all identical research objects;
5), experimental study quality evaluation:
Use Newcastle-Ottawa Scale that quality evaluation is carried out in the research of including in, main evaluate patient is selected, and withdraws from and follows up a case by regular visits to, and confirms the accuracy of biomarker state, diagnostic accuracy, the accuracy of the accuracy of prognostic indicator assessment and control Confounding Factor;
6), standardized data is processed:
Adopt standardization statistics strategy, merge measurement index, the assessment biomarker is to usefulness and the value of cancer of the stomach prognosis; If have systematic review and Meta analysis and research, directly list data in net result, otherwise carry out statistical study.Standardization statistics strategy mainly comprises: Meta analyzes, subgroup analysis, sensitivity analysis, Meta regretional analysis, heterogeneous assessment, cumulative meta-analysis, publication bias assessment;
7), prognosis biomarker screening:
Through the cancer of the stomach prognosis biomarker research that standardized data is processed, screen according to research and design method, quality of research, sample size, prognostic indicator result's conspicuousness, obtain the cancer of the stomach prognosis biomarker with potential using value;
Screening criteria is as follows: (1) has a series of randomized controlled trials, merges this amount of sample＞=500 examples, and the prognostic indicators such as OS, clinical pathologic characteristic, PFS, recurrence, toxicity are (p＜0.05) significantly, without delivering bias (p〉0.05); (2) only has single piece of randomized controlled trial, sample size 〉=300 examples, lose visit rate＜20%, quality of research is high, and (patient originates clearly, has randomizing scheme, the information such as Staging of Gastric Cancer, molecular labeling object detecting method science is reliable, and prognostic indicator is assessed according to international standard, follows up a case by regular visits to fully, statistical method science etc.), the prognostic indicators such as OS, clinical pathologic characteristic, PFS, recurrence, toxicity remarkable (p＜0.05); (3) have a plurality of experimental studies, merge sample size 〉=1000, the prognostic indicators such as OS, clinical pathologic characteristic, PFS, recurrence, toxicity are (p＜0.05) significantly, without delivering bias (p〉0.05); (4) only has single multicenter study on large sample, this Liang of Yang＞=500 examples, lose visit rate＜20%, quality of research high (patient originates clearly, the information such as Staging of Gastric Cancer, molecular labeling object detecting method science is reliable, the prognostic indicator assessment is according to international standard, follow up a case by regular visits to fully statistical method science etc.), the prognostic indicators such as OS, clinical pathologic characteristic, PFS, recurrence, toxicity are (p＜0.05) significantly;
8), according to screening criteria, filter out the cancer of the stomach prognosis biomarker with potential using value, and describe prognostic value.
Innovative point of the present invention is:
1. with respect to single experimental study screening biomarker, this method can be rejected uncorrelated research in the data of magnanimity, maximally utilises existing research evidence, can synthetically assess the value of biomarker, filters out cancer of the stomach prognosis biomarker.
2. with respect to the method for finding the prognostic markers thing by traditional multicenter large sample experimental study, this method can be at faster speed, manpower and financial resources still less screens the prognosis biomarker with potential using value, makes things convenient for researchist, doctor and enterprise to use.
In sum, the present invention has utilized a kind of biomarker screening technique based on the research evidence, carries out the screening of cancer of the stomach prognosis biomarker, to reduce the screening cost, shorten screening time, reduce professional threshold, improve the using value of prognosis biomarker.
Embodiment
Embodiment 1, a kind of evidential cancer of the stomach prognosis molecule label screening technique, carry out following steps successively:
1. formulate research evidence inclusive criteria: (1) study population is patients with gastric cancer; (2) relation between assessment biomarker and the clinical effect index, the clinical effect index must be one or more in overall life cycle (OS), Progression free survival phase (PFS), chemotherapy drug susceptibility, recurrence, toxic and side effect, the clinical pathologic characteristic etc.; (3) biomarker is one or more in gene mutation, gene pleiomorphism, mrna expression level, protein expression level, microRNA and the little satellite; (4) provide clear and definite biomarker object detecting method; (5) research and design must randomised controlled trials, cross sectional studies, cohort study or systematic review (satisfying above-mentioned at least a), be divided into perspective study and retrospective study.Get rid of following research: (1) does not have control group; (2) without the molecular labeling object detecting method; (3) research that repeats; (4) cell or zoopery; (5) survey article; (6) do not study biomarker and relationship with gastric cancer prognosis.
2. systematicness is retrieved the relevant research evidence of cancer of the stomach prognosis biomarker, and database comprises PubMed, Embase, CBM, CNKI and all places database.PubMed and Embase databases retrieval formula is : ("Stomach" OR "Gastric") AND ("cancer" OR "cancers" OR "tumor" OR "tumors" OR "neoplasm" OR "neoplasms" OR "adenoma" OR "adenomas "OR" carcinoma "OR" carcinomas "OR" adenocarcinoma "OR" adenocarcinoma "OR" malignant "OR" malignancy ") AND (" response "OR" survival "OR" outcome "OR" resistance "OR" outcomes "OR" recurrence "OR" relapse "OR" toxicity "OR" responder "OR" responders "OR" adverse events "OR" adverse event "OR" adverse effect "OR" adverse effects "OR" prognosis "OR" prognostic "OR" predictive ") AND ("polymorphism" OR "polymorphisms" OR "polymorphic" OR "genetic variant" OR "genetic variants" OR "mutation" OR "muton" OR "mutations" OR "mutons" OR "expression" OR "expressions" OR "express "OR" mrna "OR" biomarker "OR" biomarkers "OR" microsatellite "OR" microsatellites "OR" allele "OR" gene "OR" protein "OR" MicroRNAs "OR" miRNAs "OR" miRNA "OR" Micro RNA " OR "RNA; Micro" OR "MicroRNA" OR "pri-miRNA" OR "RNA; Small Temporal" OR "Temporal RNA, Small" OR "stRNA" OR "Small Temporal RNA" OR "pre-miRNA"); CBM, CNKI Wanfang database and retrieval formula is: ( " cancer " OR "stomach cancer" OR "gastric cancer") AND (" sensitivity " OR " survival " OR " survival " OR "PFS" OR "OS" OR " survival "OR" response "OR" responder "OR" outcome "OR" relapse "OR" recurrence "OR" relapse "OR" toxicity "OR" side effects "OR" prognosis "OR" forecast "OR" prognosis "OR" prognostic " OR "predictive" OR "adverse event" OR "adverse effect" OR " metastasis " OR " efficacy " OR " drug reaction ") AND (" polymorphism " OR " mutation " OR " micro- satellites " OR " expression " OR " biomarkers " OR " molecular markers " OR "polymorphism" OR "mutation" OR "expression" OR "mrna" OR "biomarker" OR "microsatellite" OR "MicroRNAs" OR "miRNA").Only retrieval is with the research of artificial research object, and research type and publication language are unrestricted.The list of references of research is included in retrieval in.
3. preliminary screening prognosis biomarker
(1) according to research evidence result for retrieval (being the result of above-mentioned steps 2 gained), according to the evidence inclusive criteria, makes up cancer of the stomach prognosis biomarker database.
(2) filter out the label with randomized controlled trial or research quantity 〉=3 and research sample size 〉=500.Wherein randomized controlled trial is undertaken obtaining behind a plurality of database retrievals by directly retrieval type being limited, and research quantity and research sample size are obtained by the statistical study of result for retrieval.The research relevant with the cancer of the stomach prognosis has 13 such as the Cdx2 expression, and total sample size is greater than 1500 examples.
The remarks explanation: this step is the preliminary screening label, according to this step, has screened one of them Cdx2, and the back is analyzed as an example of Cdx2 example.
(3) and then to the Cdx2 that screens carry out PubMed, Embase, CNKI, CBM and incomparably the research evidence of database retrieve again, retrieval type includes only cancer of the stomach and two contents of Cdx2 label, to obtain more full research evidence.retrieval type is:, (, (, (" Stomach " OR " Gastric ") AND, (" cancer " OR " cancers " OR " tumor " OR " tumors " OR " neoplasm " OR " neoplasms " OR " adenoma " OR " adenomas " OR " carcinoma " OR " carcinomas " OR " adenocarcinoma " OR " adenocarcinoma " OR " malignant " OR " malignancy ")) OR " cancer of the stomach ") AND, (" CDX2 " OR " CDX-2 " OR " caudal type homeobox 2 " OR " CDX3 " OR " CDX-3 ").Result for retrieval obtains 616 pertinent literatures, wherein meets 13 researchs that have of research evidence inclusive criteria.
4. independent of 13 researchs that meet inclusive criteria by 2 researchers, carry out research data and extract.The data content of extracting is checked, adopted consistent content, if inconsistent situation occurs, transfer to the 3rd researcher and determine.The main data of extracting comprises: the research author, deliver the time, research object source (hospital, the area, country and race etc.), patient's the baseline case (age, sex etc.), the research sample size, whether cancer of the stomach is confirmed through tissue or pathology, cancer of the stomach by stages with the differentiation situation, experimental study design detects the method for Cdx2 expression, whether adopted blind method, whether the standard of Cdx2 feminine gender and positive expression implements radiotherapy or chemotherapeutic treatment, OS, recurrence, clinicopathologic features (sex, age, knub position, clinical stages, Tumor Differentiation, vessel invasion, lymphatic metastasis) prognostic indicator such as, follow up a case by regular visits to the time, statistical analysis technique etc.
The remarks explanation: the standard compliant research that step 4 screens step 3, extract data, be used for the analysis of subsequent step 5 and 6.
5. use Newcastle-Ottawa Scale to 13 researchs including in (namely according to result for retrieval, meet 13 researchs of Cdx2 of the 1st step inclusive criteria) carry out quality evaluation, main evaluation patient selection, withdraw from and follow up a case by regular visits to, confirm the accuracy of biomarker state, diagnostic accuracy, the accuracy of the accuracy of curative effect evaluation and control Confounding Factor.Newcastle-Ottawa Scale is for the selection of research sample, comparability and result of study three class indexs, and totally 8 projects are carried out the quality of research assessment.Wherein, the research sample selects that 4 projects are arranged, and result of study has 3 projects, each project each 1 minute; Comparability has 1 project, the highest getting 2 minutes.Altogether in 9 minutes, obtained 6 minutes and above research is high-quality research, otherwise be inferior quality research.If research is high-quality research, carries out standardized data and process and analyze; If research is inferior quality research, directly this research is given up.13 researchs that the Cdx2 expression of including in is relevant all are high-quality research, are used for standardized data and process.
6. standardized data is processed
Adopt standardization statistics strategy, merge measurement index, synthetically assess biomarker to the cancer of the stomach prognostic value.Data are processed and are divided into two parts: at first assess Cdx2 expression and the relation between overall life cycle; Then analyze the relation of Cdx2 expression and clinicopathologic features, comprise sex, age, tumor size, knub position, tissue differentiation, invasion depth, vessel invasion, lymph node status, DISTANT METASTASES IN and TNM by stages.
(1) relation between Cdx2 expression and the cancer of the stomach prognosis is assessed with RR and HR and 95% fiducial interval, and wherein RR is used for assessing two classification indicators, and HR is used for assessing index life cycle.HR calculates by original data or Kaplan-Meier survivorship curve and obtains.
(2) heterogeneity between Q statistic Inspection Research.Because it is lower that statistics is renderd a service, with level of significance location 0.10.If exist significantly heterogeneous between research, adopt fixed-effect model (Variance Method or Mantel – Haenszel method) that RR or HR value are merged, if between the research remarkable heterogeneity is arranged, adopt random-effect model (DerSimonian and Laird method).The Z statistic is used in the check that merges RR or HR value.
(3) further use I
2Statistic is come the heterogeneity between the Inspection Research.The evidence quantity that the size of Q value depends on the dispersion degree of pooled variance, effect value and includes research in changes I along with the variation of evidence number
2Statistic is to have utilized degree of freedom to proofread and correct the impact of research evidence number on the Q value.Therefore the heterogeneous assay of I2 statistic announcement is more sane reliable, particularly for the chromatographic analysis of studying negligible amounts.Work as I
2, show that the variation between research is only caused by sampling error at=0 o'clock; When I2＜0.25, then think exist slight heterogeneous; Work as I
2In the time of between 0.25 and 0.5, then think to have the moderate heterogeneity; As I2〉0.5 the time, will be considered to exist height heterogeneity.
(4) subgroup analysis and Meta return and seek heterogeneous source.Meta returns and utilizes restricted maximum likelihood method to estimate weight coefficient, can integrate simultaneously the difference between research inside and the research.Because it is lower that the statistics of Meta regretional analysis is renderd a service, and the statistical significance level is decided to be 0.10.
(5) sensitivity analysis is weighed the reliability of amalgamation result by assessing individual event research or single factor for the impact of Meta analysis result.Cumulative meta-analysis is used for analyzing and merges RR or HR value along with the trend of delivering passage of time.Use funnel figure that the article publication bias is assessed, the t that further proposes with Egger checks the symmetry of qualitative assessment funnel figure.
7. prognosis biomarker screening
Through the Cdx2 expression of standardized data processing and the result of study of relationship with gastric cancer prognosis, screen according to research and design method, quality of research, sample size, prognostic indicator result's conspicuousness.
(1) 13 independent experiments have been included in research altogether in, comprise 1513 routine patients with gastric cancer, and each quality of research is better, has assessed the relation between Cdx2 expression and 5 years overall life cycles and the Clinicopathological Parameters.
(2) 5 years of Cdx2 positive expression and raising overall life cycles, conspicuousness was associated, and merging HR is 2.22(95% CI:1.78-2.75, P＜0.001).
(3) the biological table property of the aggressive of Cdx2 expression and cancer of the stomach significant correlation (sex, neoplasm staging, Tumor Differentiation, vessel invasion and lymphatic metastasis).Cdx2 positive expression patient has lower vessel invasion and lymphatic metastasis risk.
(4) sensitivity analysis shows that the relation of Cdx2 expression and cancer of the stomach prognosis is reliable, and publication bias possibility very little (P〉0.05) has shown result's confidence level.
8. according to screening criteria, it is a cancer of the stomach prognosis biomarker with potential using value that screening obtains the Cdx2 expression.5 years overall life cycles of Cdx2 positive expression and lower vessel invasion and lymphatic metastasis, raising are significantly related.In addition, a plurality of cancer of the stomach prognosis biomarkers have also been screened by this method, such as the E-cadherin expression, TYMS 2R/3R polymorphism, GSTP1 Ile105Val polymorphism, telomerase is active, the vegf expression level, MMP-9 expression, HER-2/neu expression etc.
9. carry out demonstration test, the Cdx2 expression is verified as cancer of the stomach prognosis biomarker.The retrospective 100 routine patients with gastric cancer of including in are continuously analyzed its Cdx2 expression and the relation between 5 years overall life cycles.Adopt the modeling statistics of Cox proportional distribution to analyze, the result shows that Cdx2 positive expression and raising 5 years overall life cycle of conspicuousness is associated, and HR is 1.99(95% CI:1.27-3.13).This result is consistent with the result that screening technique draws, and shows the reliability of this method.
At last, it is also to be noted that, what more than enumerate only is several specific embodiments of the present invention.Obviously, the invention is not restricted to above embodiment, many distortion can also be arranged.All distortion that those of ordinary skill in the art can directly derive or associate from content disclosed by the invention all should be thought protection scope of the present invention.
Claims (5)
1. evidential cancer of the stomach prognosis molecule label screening technique is characterized in that may further comprise the steps:
1), be the experimental study formulation inclusive criteria of cancer of the stomach prognosis biomarker:
Being included in research and design, study population, clinical effect index, these aspects of biomarker species limits;
2), formulate research evidence search strategy:
Retrieve the Clinical Evidence database comprehensively and systematically, comprise PubMed, Embase, CBMdisc (CBM), incomparably database and the total storehouse of Chinese knowledge resource (CNKI); Only retrieval is with the research of artificial research object, and research type and publication language are unrestricted; The list of references of research is included in retrieval in;
3), preliminary screening prognosis biomarker:
The research evidence that retrieves according to inclusive criteria, is determined kind and the quantity of cancer of the stomach prognosis biomarker, make up the biomarker database;
Biomarker screens according to the quantity of research and design method, research and the sample size of research, and filter out the biomarker that satisfies following any one condition: (1) has randomised controlled trials; (2) research quantity 〉=3 and research sample size 〉=500;
4), research data extracts:
Independently carry out data by 2 researchers according to the research data extraction content that pre-establishes and standard and extract and cross check, guarantee that research data extracts and the result of quality assessment has consistance, transfer to the 3rd researcher when at sixes and sevens and determine;
5), experimental study quality evaluation:
Use Newcastle-Ottawa Scale that quality evaluation is carried out in the research of including in, comprise the evaluate patient selection, withdraw from accuracy, diagnostic accuracy, the accuracy of prognostic indicator assessment and the accuracy of control Confounding Factor of following up a case by regular visits to, confirm the biomarker state;
6), standardized data is processed:
Adopt standardization statistics strategy, merge measurement index, the assessment biomarker is to usefulness and the value of cancer of the stomach prognosis; If have systematic review and Meta analysis and research, directly list data in net result, otherwise carry out statistical study; Standardization statistics strategy mainly comprises: Meta analyzes, subgroup analysis, sensitivity analysis, Meta regretional analysis, heterogeneous assessment, cumulative meta-analysis, publication bias assessment;
7), prognosis biomarker screening:
Through the cancer of the stomach prognosis biomarker research that standardized data is processed, screen according to research and design method, quality of research, sample size, prognostic indicator result's conspicuousness, obtain the cancer of the stomach prognosis biomarker with potential using value;
8), according to screening criteria, filter out the cancer of the stomach prognosis biomarker with potential using value, and describe prognostic value.
2. evidential cancer of the stomach prognosis molecule label screening technique according to claim 1 is characterized in that:
The screening criteria of described step 7) is as follows: (1) has a series of randomized controlled trials, merges this amount of sample＞=500 examples, and the prognostic indicators such as OS, clinical pathologic characteristic, PFS, recurrence, toxicity are (p＜0.05) significantly, without delivering bias (p〉0.05); (2) only have single piece of randomized controlled trial, sample size 〉=300 examples is lost visit rate＜20%, and quality of research is high, and the prognostic indicators such as OS, clinical pathologic characteristic, PFS, recurrence, toxicity are (p＜0.05) significantly; (3) have a plurality of experimental studies, merge sample size 〉=1000, the prognostic indicators such as OS, clinical pathologic characteristic, PFS, recurrence, toxicity are (p＜0.05) significantly, without delivering bias (p〉0.05); (4) only have single multicenter study on large sample, this Liang of Yang＞=500 examples loses visit rate＜20%, and quality of research is high, and the prognostic indicators such as OS, clinical pathologic characteristic, PFS, recurrence, toxicity are (p＜0.05) significantly.
3. evidential cancer of the stomach prognosis molecule label screening technique according to claim 1 and 2 is characterized in that:
Described step 1) is:
Described evidence inclusive criteria is: (1) study population is patients with gastric cancer; (2) relation between assessment biomarker and the clinical effect index, the clinical effect index must be one or more in overall life cycle (OS), Progression free survival phase (PFS), chemotherapy drug susceptibility, recurrence, toxic and side effect, the clinical pathologic characteristic etc.; (3) biomarker is one or more in gene mutation, gene pleiomorphism, mrna expression level, protein expression level, microRNA and the little satellite; (4) provide clear and definite biomarker object detecting method; (5) research and design must randomised controlled trials, cross sectional studies, cohort study or systematic review (satisfying above-mentioned at least a), be divided into perspective study and retrospective study;
Get rid of following research: (1) does not have control group; (2) without the molecular labeling object detecting method; (3) research that repeats; (4) cell or zoopery; (5) survey article; (6) do not study biomarker and relationship with gastric cancer prognosis.
4. evidential cancer of the stomach prognosis molecule label screening technique according to claim 3 is characterized in that:
Described step 2) in:
PubMed and Embase databases retrieval formula is : ("Stomach" OR "Gastric") AND ("cancer" OR "cancers" OR "tumor" OR "tumors" OR "neoplasm" OR "neoplasms" OR "adenoma" OR "adenomas "OR" carcinoma "OR" carcinomas "OR" adenocarcinoma "OR" adenocarcinoma "OR" malignant "OR" malignancy ") AND (" response "OR" survival "OR" outcome "OR" resistance "OR" outcomes "OR" recurrence "OR" relapse "OR" toxicity "OR" responder "OR" responders "OR" adverse events "OR" adverse event "OR" adverse effect "OR" adverse effects "OR" prognosis "OR" prognostic "OR" predictive ") AND ("polymorphism" OR "polymorphisms" OR "polymorphic" OR "genetic variant" OR "genetic variants" OR "mutation" OR "muton" OR "mutations" OR "mutons" OR "expression" OR "expressions" OR "express "OR" mrna "OR" biomarker "OR" biomarkers "OR" microsatellite "OR" microsatellites "OR" allele "OR" gene "OR" protein "OR" MicroRNAs "OR" miRNAs "OR" miRNA "OR" Micro RNA " OR "RNA; Micro" OR "MicroRNA" OR "pri-miRNA" OR "RNA; Small Temporal" OR "Temporal RNA, Small" OR "stRNA" OR "Small Temporal RNA" OR "pre-miRNA");
CBM, CNKI and Wanfang database retrieval formula is: ("cancer" OR "stomach cancer" OR "gastric cancer") AND ("sensitivity" OR "survival" OR "survival" OR "PFS" OR "OS" OR "survival" OR "response" OR "responder" OR "outcome" OR "relapse" OR "recurrence" OR "relapse" OR "toxic" OR "side" OR "prognosis" OR "forecast" OR "prognosis" OR "prognostic "OR" predictive "OR" adverse event "OR" adverse effect "OR" metastasis "OR" efficacy "OR" drug reaction ") AND (" polymorphism "OR" mutation "OR" micro-satellites "OR" expression "OR" biomarkers "OR" molecular markers "OR" polymorphism "OR" mutation "OR" expression "OR" mrna "OR" biomarker "OR" microsatellite "OR" MicroRNAs "OR" miRNA ").
5. utilize the cancer of the stomach prognosis molecule label that gets such as any one method screening in the claim 1 ~ 4, it is characterized in that: be Cdx2.
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| CN108305667A (en) * | 2018-01-10 | 2018-07-20 | 北京大学深圳医院（北京大学深圳临床医学院） | Method of the evidential evaluation TNF-α as the biomarker of assessment Yoga curative effect |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104091062A (en) * | 2014-07-03 | 2014-10-08 | 刘鸿 | Diagnostic test Meta analysis method based on power of test |
| WO2017215230A1 (en) * | 2016-06-15 | 2017-12-21 | 南京卡迪睿伯生物技术有限公司 | Use of a group of gastric cancer genes |
| CN108305667A (en) * | 2018-01-10 | 2018-07-20 | 北京大学深圳医院（北京大学深圳临床医学院） | Method of the evidential evaluation TNF-α as the biomarker of assessment Yoga curative effect |
| WO2020258254A1 (en) * | 2019-06-28 | 2020-12-30 | 北京哲源科技有限责任公司 | Data mining method and electronic device |
| CN112567345A (en) * | 2019-06-28 | 2021-03-26 | 北京哲源科技有限责任公司 | Data mining method and electronic equipment |
| CN112567345B (en) * | 2019-06-28 | 2024-06-04 | 北京哲源科技有限责任公司 | Data mining method and electronic equipment |
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