Identification and Validation of an Individualized EMT-Related Prognostic Risk Score Formula in Gastric Adenocarcinoma Patients

Abstract

Background: The epithelial-mesenchymal transition (EMT) is a pivotal process for fibrotic disease, embryonic development, and wound healing. Moreover, some evidence has proven that the disorder of EMT also plays an important role in carcinogenesis, especially invasion and metastasis of various tumors (Ritchie et al., 2015). Additionally, gastric adenocarcinoma (GAC) is a common gastrointestinal malignancy which is the fourth most commonly diagnosed tumor. Our study is aimed at identifying the prognostic value of EMT-related genes in gastric adenocarcinoma.

Methods: Firstly, high-throughput and clinical data were downloaded from The Cancer Genome Atlas (TCGA) database. 99 differentially expressed EMT-related genes (ERGs) were obtained in these gastric adenocarcinoma data. Secondly, GO and KEGG enrichment analyses show that EMT may promote gastric carcinogenesis. Next, 10 ERGs associated with prognosis of gastric adenocarcinoma patients are screened out by univariate Cox regression, and 6 pivotal prognostic ERGs (MMP8, MMP11, TFDP3, MYB, F2, and CNTN1) are identified through multivariate Cox regression. These 6 genes are confirmed with significant prognostic value in gastric adenocarcinoma through overall survival (OS) analysis. Finally, a risk score formula is constructed and tested in another gastric adenocarcinoma cohort from GEO.

Results: 99 differentially expressed EMT-related genes (ERGs) and their enriched pathways are identified. 10 ERGs are strongly related to the prognosis of GAC patients. A risk score formula of 6 prognosis-related ERGs used to predict the prognosis of gastric adenocarcinoma patients is identified and tested (risk score = 0.448115∗expression value of MMP8 + 0.378892∗expression value of MMP11 - 0.3226∗expression value of MYB + 1.322812∗expression value of TFDP3 + 0.325063∗expression value of F2 + 0.334197∗expression value of CNTN1).

Conclusion: This study provides a potential prognostic signature for predicting prognosis of gastric adenocarcinoma patients and molecular insights of EMT in gastric adenocarcinoma, and the formula focusing on the prognosis of gastric adenocarcinoma can be effective.