Integrative analysis of the cancer genome atlas and cancer cell lines encyclopedia large-scale genomic databases: MUC4/MUC16/MUC20 signature is associated with poor survival in human carcinomas

Nicolas Jonckheere, Isabelle Van Seuningen

MUC4 is a membrane-bound mucin that promotes carcinogenetic progression and is often proposed as a promising biomarker for various carcinomas. In this manuscript, we analyzed large scale genomic datasets in order to evaluate MUC4 expression, identify genes that are correlated with MUC4 and propose new signatures as a prognostic marker of epithelial cancers. Using cBioportal or SurvExpress tools, we studied MUC4 expression in large-scale genomic public datasets of human cancer (the cancer genome atlas, TCGA) and cancer cell line encyclopedia (CCLE). We identified 187 co-expressed genes for which the expression is correlated with MUC4 expression. Gene ontology analysis showed they are notably involved in cell adhesion, cell-cell junctions, glycosylation and cell signaling. In addition, we showed that MUC4 expression is correlated with MUC16 and MUC20, two other membrane-bound mucins. We showed that MUC4 expression is associated with a poorer overall survival in TCGA cancers with different localizations including pancreatic cancer, bladder cancer, colon cancer, lung adenocarcinoma, lung squamous adenocarcinoma, skin cancer and stomach cancer. We showed that the combination of MUC4, MUC16 and MUC20 signature is associated with statistically significant reduced overall survival and increased hazard ratio in pancreatic, colon and stomach cancer. Altogether, this study provides the link between (i) MUC4 expression and clinical outcome in cancer and (ii) MUC4 expression and correlated genes involved in cell adhesion, cell-cell junctions, glycosylation and cell signaling. We propose the MUC4/MUC16/MUC20high signature as a marker of poor prognostic for pancreatic, colon and stomach cancers.