| Objective: Colorectal cancer is one of the most common and malignant tumors,and its incidence rate is the third in the world.The 2015 China Cancer Statistics show that the incidence and mortality of China colorectal cancer patients ranks 5th among all malignant tumors.There were 376,000 new cases and 191,000 deaths,and the incidence of colorectal cancer increased significantly.Because the early symptoms of colorectal cancer are not obvious,most patients with colorectal cancer are in advanced stage at the time of diagnosis.The best treatment of colorectal cancer nowadays is mainly based on surgery.many patients Loss the opportunity for radical surgery at the time of diagnosis.For patients with colorectal cancer who have undergone radical surgery and standardized chemotherapy,some cases will recurrence or metastasis after a period of time which is a problem that clinicians and patients have to face.For the patients who have recurrence or metastasis,only a small percentage of them get the chance for re-surgically resected.Most patients with advanced colorectal cancer may not be able to tolerate standardized chemotherapy.Even if they can tolerate chemotherapy,those drugs may be insensitive and disease may have progression.Patients with metastatic colorectal cancer have a poor prognosis.some of them will benefit from The anti-epidermal growth factor receptor(EGFR)monoclonal antibody.The National Comprehensive Cancer Network(NCCN)guidelines for colorectal cancer diagnosis and treatment indicate: 1.the KRAS gene Mutations of the 12 and 13 codons in second exon indicate that monoclonal antibodies against EGFR,such as cetuximab and panitumumab,are ineffective.And more recent evidence suggests that mutations other than the second exon of the KRAS gene and mutations in the NRAS gene can also predict the ineffective of cetuximab and panitumumab treatment.Therefore,the expert group strongly recommends for all metastatic knots.It is necessary to detect KRAS gene/NRAS gene mutation in tumor tissues(either primary tumor or metastases)of patients with colorectal cancer.Patients with known KRAS/NRAS mutations should not receive cetuximab or panitumumab,either alone or in combination with chemotherapy;2.Recommended cetuximab or panitumumab to treated patients with colorectal cancer who are wild type of KRAS gene;3.Existing clinical studies have shown that anti-EGFR therapy has no effect in the treatment of stage I/II/III colon cancer;4.KARS gene mutation is considered to be an early event of tumorigenesis,And has been in the early state.[1] For advanced patients with colorectal cancer,it is undoubtedly painful to obtain tumor tissue by surgery or biopsy to determine the state of KRAS gene.We prefer to obtain results more efficiently in a minimally invasive or even non-invasive manner.In recent years,more studies on the status of KRAS genes in colorectal cancer patients detected by circulating cell-free nucleic acid have been reported,but the results reported by various studies are quite different.Only three of the reports have been comprehensively analyzed and the deadline of collection data is June 2016 [2-4],and through literature search,we found that more studies have published after June 2016,and the mentioned three studies included patients with various stage of colorectal cancer patients.The database in two studies contained only English database,which may lead to bias in their results.Based on Cochrane recommended that update interval of meta-analysis is two years,and in order to further clarify the diagnostic value of KRAS gene mutation status detected by circulating cell-free nucleic acid in colorectal cancer patients with stage IV,we conducted this metaanalysis.Methods: The relevant literatures were obtained by searching 6 databases of Embase,Cochrane,PubMed,CBM,Wanfang and CNKI.The inclusion criteria were as follows: 1.Patients diagnosed with stage IV colorectal cancer;2.All patients included who confirm KRAS gene status both in colorectal cancer Tumor tissue(surgery or biopsy)and circulating cell-free nucleic acid;3.Inclusion studies can extract true positive number(TP),false positive number(FP),false negative number(FN),true negative number(TN)and other related data.By extracting data into a 2×2 contingency table,the combined sensitivity,specificity,positive likelihood ratio(LR+),negative likelihood ratio(LR-),diagnostic odds ratio(DOR),ROC curve and other related statistical indicators were calculated..The publication bias of the literature was obtained by Deek’s graph symmetry test,and the diagnostic efficacy of the circulating cell-free nucleic acid for detecting the KRAS gene mutation status was further evaluated by the fagan plot and the likelihood ratio matrix map.Finally,a subgroup analysis is used to discuss factors that may lead to heterogeneity.Results: In a diagnostic experiment to assess the state of circulating cell-free nucleic acid for detecting KRAS gene mutations,a total of 48 studies were included,totaling 3,836 samples.The total KRAS gene mutated sample determined by the gold standard was 1758,and the unmutated sample was 2078.The combined sensitivity,specificity,LR+,LR-,DOR were 0.79 [95% CI: 0.73,0.84],0.93 [95% CI: 0.90,0.95],11.5 [95% CI: 8.0,16.4] 0.23 [ 95% CI : 0.17,0.29] and 51 [95% CI: 33,79].The area under the ROC curve is 0.94 [95% CI: 0.91,0.96].Compared with the pre-test probability of 46%,the positive post-test probability is 91%,suggesting that the circulating free nucleic acid has a good diagnostic efficiency,and the subgroup analysis shows that the practical plasma is more effective than the serum.Conclusion: Detection of KRAS gene mutation status in patients with colorectal cancer by circulating cell-free nucleic acid has high diagnostic accuracy and can be used as a substitute for tissue samples for detection of KRAS mutation state in advanced colorectal cancer patients.. |
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