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Characterization of a five-microRNA signature as a prognostic biomarker for esophageal squamous cell carcinoma.

ABSTRACT: This study aims to identify a miRNAs signature for predicting overall survival (OS) in esophageal squamous cell carcinoma (ESCC) patients. MiRNA expression profiles and corresponding clinical information of 119 ESCC patients were obtained from NCBI GEO and used as the training set. Differentially expressed miRNAs (DEmiRNAs) were screened between early-stage and late-stage samples. Cox regression analysis, recursive feature elimination (RFE)-support vector machine (SVM) algorithm, and LASSO Cox regression model were used to identify prognostic miRNAs and consequently build a prognostic scoring model. Moreover, promising target genes of these prognostic miRNAs were predicted followed by construction of miRNA-target gene networks. Functional relevance of predicted target genes of these prognostic miRNAs in ESCC was analyzed by performing function enrichment analyses. There were 46 DEmiRNAs between early-stage and late-stage samples in the training set. A risk score model based on five miRNAs was built. The five-miRNA risk score could classify the training set into a high-risk group and a low-risk group with significantly different OS time. Risk stratification ability of the five-miRNA risk score was successfully validated on an independent set from the Cancer Genome Atlas (TCGA). Various biological processes and pathways were identified to be related to these miRNAs, such as Wnt signaling pathway, inflammatory mediator regulation of TRP channels pathway, and estrogen signaling pathway. The present study suggests a pathological stage-related five-miRNA signature that may have clinical implications in predicting prognosis of ESCC patients.

SUBMITTER: Yu J

PROVIDER: S-EPMC6934627 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Project description:Background and aimsMicroRNAs including miR146a have a regulatory role on the expression of genes and act with binding to 3'-UTR region of the genes. Cyclooxygenase-2 (COX-2) is involved in carcinogenesis as an inflammatory marker, and microRNA-146a (miR-146a) as a negative regulatory factor. We aimed to evaluate miR146a expression as a prognostic or diagnostic biomarker for esophageal squamous cell carcinoma (ESCC) and also an association between miR146a and COX2 expression.Materials and methodsWe quantified the level of miR-146a and COX-2 expression in cancerous and adjacent normal tissue samples obtained from 34 patients with ESCC, using real-time-PCR. Statistical analyses were conducted using one-sample t-test. Receiver-operating characteristic (ROC) curve and Kaplan-Meier analysis were applied to assay miR146a as a diagnostic and prognostic marker, respectively, during 4 years of the study. Furthermore, the Cox regression model was performed to assay the hazard ratio (HR). The association between miR-146a and COX2 expression level in ESCC patients was evaluated by nonparametric Spearman's rho analysis.ResultsThe results revealed a reduction of miR-146a expression in 50% of cancerous tissue when compared with adjacent normal regions (P-value=0.127). COX-2 expression in 80% of ESCC patients was higher than in the controls (P-value=0.001). Overall, in 60% of cases, direct association was seen between microRNA-146a and COX-2 expression level (correlation coefficient= 0.438, P-value=0.011). COX2 can be considered as a diagnostic biomarker (AUC=0.834, sensitivity=72%, specificity =83%, P-value<0.0001) but miR146a cannot be considered as a diagnostic biomarker (AUC=0.553, sensitivity=88%, specificity =28%, P-value=0.453). Survival analysis by Kaplan-Meier method showed miR146a and COX2 expression can be probably considered as prognostic biomarkers for ESCC because patients with high expression of miR146a had 7 months shorter life span and patients with low expression of COX2 had 8 months shorter life span.ConclusionCOX2 expression is a diagnostic biomarker. MiR-146a and COX2 expression can probably be considered as prognostic biomarkers for survival in ESCC.

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Characterization of a five-microRNA signature as a prognostic biomarker for esophageal squamous cell carcinoma.

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