Dataset Information

Validation of miRNA prognostic significance in stage II colorectal cancer: A protocol for systematic review and meta-analysis of observational clinical studies.

ABSTRACT:

Background

Advances in early detection and treatment of colorectal cancer (CRC) has seen marked improvements in recent years. However, it is still the third leading cause of cancer-related deaths worldwide. Although there are studies reporting the significance of miRNAs in stage II colorectal cancer, there is no known comprehensive study utilising collective data from multiple published studies. Thus, this study will focus on performing a systematic review and meta-analysis using published data to identify and underline multiple miRNA targets, with regard to disease prognosis in stage II CRC patients.

Methods

The systematic review will be reported according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, 2015 statement. The required articles will be obtained via a search of bibliographical databases such as Cochrane Library, EMBASE, MEDLINE, PubMed, and Web of Science. A set of keywords in multiple permutations will be used for the search. The reference lists of included studies will also be manually searched to further increase the robustness of the search results. The systematic review will primarily be done via a literary synthesis.

Results

Quantitative data synthesis will be based on estimated effect across the studies with forest plots generated to observe pooled outcome measures. A fixed or random-effect model of meta-analysis will be used depending upon the heterogeneity observed between studies. Subgroup analysis will be carried out depending on the availability of sufficient clinical data.

Conclusion

Based on the systematic review and meta-analysis results of this study, the possible miRNAs could be predicted toward the prognosis of stage II colorectal cancer, and specific miRNAs may perhaps be considered as a biomarker and therapeutic target for this malignancy.

SUBMITTER: Sabarimurugan S

PROVIDER: S-EPMC6709282 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Publications

Validation of miRNA prognostic significance in stage II colorectal cancer: A protocol for systematic review and meta-analysis of observational clinical studies.

Sabarimurugan Shanthi S Kumarasamy Chellan C Madurantakam Royam Madhav M Lakhotiya Karthik K Kodiveri Muthukaliannan Gothandam G Ramalingam Suja S Jayaraj Rama R

Medicine 20190301 12

<h4>Background</h4>Advances in early detection and treatment of colorectal cancer (CRC) has seen marked improvements in recent years. However, it is still the third leading cause of cancer-related deaths worldwide. Although there are studies reporting the significance of miRNAs in stage II colorectal cancer, there is no known comprehensive study utilising collective data from multiple published studies. Thus, this study will focus on performing a systematic review and meta-analysis using publish ...[more]

PMID: 30896613

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Project description:Currently, there is no consensus about the use of adjuvant chemotherapy for patients with stage II colorectal cancer. Here, we aimed to identify and validate a prognostic mRNA expression signature for the stratification of patients with stage II colorectal cancer according to their risk for relapse. First, publicly available mRNA expression profiling datasets from 792 primary, stage II colorectal cancers from six different training cohorts were analyzed to identify genes that are consistently associated with patient relapse-free survival (RFS). Second, the identified gene expression signature was experimentally validated using NanoString technology and computationally refined on primary colorectal cancer samples from 205 patients with stage II colorectal cancer. Third, the refined signature was validated in two independent publicly available cohorts of 166 patients with stage II colorectal cancer. Bioinformatics analysis of training cohorts identified a 61-gene signature that was highly significantly associated with RFS (HR = 37.08, P = 2.68*10-106, sensitivity = 89.29%, specificity = 89.61%, and AUC = 0.937). The experimental validation and refinement revealed a 15-gene signature that robustly predicted relapse in three independent cohorts: an in-house cohort (HR = 20.4, P = 8.73*10-23, sensitivity = 90.32%, specificity = 80.99%, AUC = 0.812), GSE161158 (HR = 5.81, P = 3.57*10-4, sensitivity = 64.29%, specificity = 81.67%, AUC = 0.796), and GSE26906 (HR = 7.698, P = 7.26*10-8, sensitivity = 61.54%, specificity = 78.33%, AUC = 0.752). In the pooled training cohort, the 15-gene signature (HR = 4.72, P = 7.76*10-25, sensitivity = 75%, specificity = 67.44%, AUC = 0.784) was superior to the Oncotype DX colon 7-gene signature (HR = 2.698, P = 6.3*10-8, sensitivity = 62.16%, specificity = 55.5%, AUC = 0.633). We report the identification and validation of a novel mRNA expression signature for robust prognostication and stratification of patients with stage II colorectal cancer, with superior performance in the analyzed validation cohorts when compared with clinicopathologic biomarkers and signatures currently used for stage II colorectal cancer prognostication.SignificanceWe identified and validated a 15-gene expression signature for robust prognostication and stratification of patients with stage II colorectal cancer, with superior performance when compared with currently used biomarkers. Therefore, the 15-gene expression signature has the potential to improve the prognostication and treatment decisions for patients with stage II colorectal cancer.

Project description:BACKGROUND:The development of colorectal cancer (CRC) is a complicated multistep process that involves an accumulation of mutations in tumor suppressor genes and oncogenes. In the process of DNA replication, base mismatch often occurs due to various factors leading to abnormal expression of mismatch repair genes (MMR), among which MLH1 and MSH2 are the most important. Recently, numerous studies indicated that MLH1/MSH2 phenotype is associated with CRC. We wanted to elucidate the role of MLH1/MSH2 in the prediction and prognosis of CRC through long-term clinical observation. AIM:To evaluate the prognostic and predictive significance of MLH1/MSH2 in patients with stage II-III CRC using immunohistochemical analysis and GeneScan. METHODS:Specimens from 681 patients with CRC (395 stage II and 286 stage III, 387 males and 294 females) who underwent curative surgical resection from 2013 to 2016 were tested. Immunohistochemistry was used to analyze MMR status and the microsatellite status of 133 patients was determined by GeneScan analysis. RESULTS:Five hundred and fifty (80.76%) patients were MLH1/MSH2 positive and 131 (19.24%) were negative by immunohistochemistry. MLH1/MSH2-positive tumors were significantly more frequent in the colon than in the rectum, and had poor differentiation and less mucin production (P < 0.05). Patients of different groups did not differ in terms of age, gender, tumor size, tumor stage, lymphocytic infiltration, or circumscribed margin. MLH1/MSH2-negative patients had a more favorable OS than MLH1/MSH2-positive patients (P < 0.001). Univariate and multivariate analyses demonstrated MLH1/MSH2 expression as an independent prognostic and predictive factor for stage II/III CRC. MLH1/MSH2 expression was a strong prognostic factor in all patients [P < 0.001, hazard ratio (HR) = 4.064, 95%CI: 2.241-7.369]. Adjuvant chemotherapy had a greater correlation with survival advantage in MLH1/MSH2-negative patients with stage III disease (P < 0.001, HR = 7.660, 95%CI: 2.974-15.883). However, patients with stage II disease or MLH1/MSH2-positive patients with stage III disease did not benefit from adjuvant chemotherapy. GeneScan analysis demonstrated that among 133 patients, 105 (78.95%) were microsatellite stable, and 28 (21.05%) had microsatellite instability (MSI), including 18 (13.53%) with high MSI and 10 (7.52%) with low MSI. This is consistent with the immunohistochemical results. CONCLUSION:MLH1/MSH2 phenotype constitutes a pathologically and clinically distinct subtype of sporadic CRC. MLH1/MSH2 is an independent prognostic and predictive factor for outcome of stage II-III CRC.

Dataset Information

Validation of miRNA prognostic significance in stage II colorectal cancer: A protocol for systematic review and meta-analysis of observational clinical studies.

Background

Methods

Results

Conclusion

Publications

Validation of miRNA prognostic significance in stage II colorectal cancer: A protocol for systematic review and meta-analysis of observational clinical studies.

Similar Datasets

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