Abstract
BackgroundThe epithelial-mesenchymal transition (EMT) plays a pivotal role in various physiological processes, such as embryonic development, tissue morphogenesis, and wound healing. EMT also plays an important role in cancer invasion, metastasis, and chemoresistance. Additionally, EMT is partially responsible for chemoresistance in colorectal cancer (CRC). The aim of this research is to develop an EMT-based prognostic signature in CRC.MethodsRNA-seq and microarray data, together with clinical information, were downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. A total of 244 differentially expressed EMT-related genes (ERGs) were obtained by comparing the expression between normal and tumor tissues. An EMT-related signature of 11 genes was identified as crucially related to the overall survival (OS) of patients through univariate Cox proportional hazard analysis, least absolute shrinkage and selection operator (LASSO), and Cox regression analysis. Finally, we established a clinical nomogram to predict the survival possibility of CRC patients by integrating clinical characteristics and the EMT-related gene signature.ResultsTwo hundred and forty-four differentially expressed ERGs and their enriched pathways were confirmed. Significant enrichment analysis revealed that EMT-related signaling pathway genes were highly related to CRC. Kaplan-Meier analysis revealed that the 11-EMT signature could significantly distinguish high- and low-risk patients in both TCGA and GEO CRC cohorts. In addition, the calibration curves verified fine concordance between the nomogram prediction model and actual observation.ConclusionWe developed a novel EMT-related gene signature for the prognosis prediction of CRC patients, which could improve the individualized outcome prediction in CRC.
Highlights
The epithelial-mesenchymal transition (EMT) plays a pivotal role in various physiological processes, such as embryonic development, tissue morphogenesis, and wound healing
A growing number of studies have shown that the epithelial-mesenchymal transition (EMT) plays an important role in invasion, metastasis, and chemoresistance [5,6,7,8,9]
The results showed that colorectal cancer (CRC) patients with high EMT risk scores were obviously associated with shorter overall survival (OS) than that of patients with low risk scores
Summary
The epithelial-mesenchymal transition (EMT) plays a pivotal role in various physiological processes, such as embryonic development, tissue morphogenesis, and wound healing. EMT plays an important role in cancer invasion, metastasis, and chemoresistance. EMT is partially responsible for chemoresistance in colorectal cancer (CRC). Colorectal cancer (CRC) remains the third leading cause of cancer-related deaths worldwide [1]. The diverse prognosis of CRC patients might be due to the inherent genetic heterogeneity. A growing number of studies have shown that the epithelial-mesenchymal transition (EMT) plays an important role in invasion, metastasis, and chemoresistance [5,6,7,8,9]. Even though the mechanisms of EMT have been extensively studied in CRC, the prognostic value of ERGs remains limited and inconclusive
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