Identification of CERS5 as a molecular biomarker in pan-cancer through multiple omics integrative analysis

Abstract

Cancer is a devastating disease that presents a major threat to human health. The protein CERS5 is responsible for synthesizing C16-ceramide, but its role in cancer is poorly understood. In this study, we examined the connection between CERS5 expression and pan-cancer prognosis, diagnosis, and the molecular mechanism involved. Kaplan-Meier survival analysis revealed variations among different cancer types. Functional enrichment analysis was conducted using gene set enrichment analysis (GSEA), and a network of protein–protein interaction (PPI) was constructed. The relationship between CERS5 and 22 immune infiltrating cell categories was detected using CIBERSORT. Single-cell analysis revealed elevated CERS5 levels in fibroblasts, which are vital in tumor immunity. The relationship between the expression of CERS5 and the immune-related genes, microsatellite instability, tumor mutational burden, and RNA modification genes in cancer were examined using the pan-cancer database. The role of CERS5 in immune regulation might be crucial to the tumor microenvironment. Pathway enrichment analysis indicated associations between CERS5 and extracellular matrix–receptor interaction, the WNT signaling pathway, and cell–cell junctions. Specifically, CERS5 was positively correlated with Cytotoxic T-Lymphocyte Associated Protein 4 (CTLA4), Programmed Cell Death 1 (PDCD1), and Lymphocyte Activating 3 (LAG3) in stomach adenocarcinoma. In vitro, knockdown of CERS5 significantly hindered gastric cancer cells' ability to proliferate, migrate invade and increased apoptotic rate. We believe that CERS5 could be a promising target for future cancer research, contributing to the development of effective therapies.