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

Abstract

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.

Unsupervised Hierarchical Clustering of Pancreatic Adenocarcinoma Dataset from TCGA Defines a Mucin Expression Profile that Impacts Overall Survival

“…We hypothesize that the MUC14/MUC18/MUC15 subgroup could overlap with the different stromal populations. Recent work also showed that the expression levels of MUC14/EMCN , MUC18/MCAM , and MUC15 individually showed significant correlations with worse overall survival in stomach adenocarcinoma (STAD) from TCGA dataset [ 27 ] suggesting that these genes could also be prognostic biomarkers in other digestive cancers. However, this could be specific to gastric cancer since we observed that MUC14 and MUC18 are associated with better survival in the PDAC cohort.…”

“…Two additional atypical endothelial mucins (MUC14/EMCN and MUC18/MCAM) have been described in cancer [ 25 , 26 ]. MUC14, also known as endomucin (EMCN), is an endothelial sialomucin that inhibits endothelial–leukocyte interaction and has been reported to be a poor prognosis marker in gastric cancer [ 27 ]. MUC18 also called melanoma cell adhesion molecule (MCAM) or CD146, is a glycoprotein that is associated with gallbladder cancer and melanoma and that is also detected in pancreatic cancer stroma [ 28 ].…”

Research progress on the structure and function of endomucin

“…Further studies confirming this role could provide a new molecular mechanism for abnormal angiogenesis and a new target for inhibiting the growth of abnormal blood vessels in clinical tumor therapy. Recently, a systematic analysis of the cancer genome database showed that combined detection of EMCN/MUC15 may be a potential prognostic marker for gastric cancer 31 …”

High Expression of MUC15 Is Correlated with Poor Prognosis of Pancreatic Cancer and Promotes Migration, Invasion, and Chemo-Resistance In Vitro

“…Survival data on MUC15 in PDAC from TCGA database also agrees with our results. Dai [ 34 ], analyzing TCGA, also reported that MUC15 combined with EMCN is a prognostic signature for gastric cancer. Because membrane MUC15 in our study was only positive in 37 of 92 samples, we failed to draw a strong conclusion about the relationship between membrane MUC15 and clinicopathological parameters, and larger immunohistochemistry studies are needed to explore its prognostic value.…”