Construction of epithelial-mesenchymal transition related miRNAs signatures as prognostic biomarkers in gastric cancer patients

Abstract

Aim: To identify the potential post-healing EMT related miRNAs associated with lymph node metastatic gastric cancer (LNMGC). Methods: Both RNA expression and clinical medical data were obtained from the TCGA dataset. We performed differential expression and normalization analysis of miRNAs. Cox linear regression model confirmed the differentially expressed miRNAs (DEmiRNAs) and clinical medical parameters related to overall survival (OS). The role of target genes of DEmiRNAs was determined according to the role enrichment analysis. Results: We obtained a total of 7531 DEmRNAs and 267 DEmRNAs, of which 185 DEmRNAs were down-regulated and 82 DEmRNAs were up-regulated. We randomly divided the LMNGC cases (n=291) into a training group (n=207) and a test group (n=84). The results showed that a total of 103, 11, 13 and 83 overlapping genes were associated with hsa-mir-141-3p, hsa-mir-4664-3p, hsa-mir-125b-5p and hsa-mir-7-5p, respectively. Kaplan-Meier determined that these four miRNAs can effectively distinguish high-risk and low-risk groups, and have a good indicator role (all p<0.05). Multivariate cox regression analysis also showed that EMT-related miRNA predictive model and lymph node metastasis were both prognostic risk factors (all p<0.05). The ROC curve showed that this feature had high accuracy (AUC>0.7, p<0.05). In addition, KEGG analysis showed that EMT-related pathways were mainly enriched in HIF-1 signaling pathway and focal adhesion. Conclusions: Our study demonstrated that EMT-related miRNAs could serve as independent prognostic markers in pN 1-3 GC patients.