Systematical Analysis of the Cancer Genome Atlas Database Reveals EMCN/MUC15 Combination as a Prognostic Signature for Gastric Cancer

Digestive cancers-including gastric cancer (GC), colorectal cancer, hepatocellular carcinoma, esophageal cancer, and pancreatic cancer-accounted for 26% of cancer cases and 35% of cancer deaths worldwide in 2018. It is crucial and urgent to develop biomarkers for the diagnosis, prognosis, and therapeutic benefits of digestive cancers, especially for GC, since the incidence of GC is lower only than lung cancer in China, is hard to detect at an early stage, and is associated with poor prognosis. Mucins, glycoproteins encoded by MUC family genes, act as a part of a physical barrier in the digestive tract and participate in various signaling pathways. Some mucins have been used or proposed as biomarkers for carcinomas, such as MUC16 (CA125) and MUC4. However, there are no systematic investigations on the association of MUC family members with diagnoses and clinical outcomes even though relevant data have been largely accumulated in the past decade. By analyzing transcriptomic and clinical data of digestive cancer samples from TCGA involving colon adenocarcinoma (COAD), esophageal carcinoma (ESCA), liver hepatocellular carcinoma (LIHC), stomach adenocarcinoma (STAD), and pancreatic adenocarcinoma (PAAD), it was found that expressions levels of MUC15, MUC13, and MUC21 were individually associated with survival for digestive cancers, and high expressions of EMCN (MUC14) and MUC15 were correlated with poor survival for STAD. Cox regression analysis indicated the predictive power of an EMCN/MUC15 combination for overall survival (OS) of GC patients, which was validated on an independent dataset from GEO. EMCN/MUC15 correlated genes were identified to be enriched in cancer-related processes, such as vasculature development, mitosis, and immunity. Therefore, we propose that an EMCN/MUC15 combination could be a potential prognostic signature for gastric cancer.