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

Cell Signal. 2024 Apr:116:111054. doi: 10.1016/j.cellsig.2024.111054. Epub 2024 Jan 18.

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.

Keywords: CERS5; Drug sensitivity; Immune infiltration; Pan-cancer; Prognosis; STAD; Single cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma*
  • Biomarkers
  • Fibroblasts
  • Humans
  • Stomach Neoplasms*
  • Tumor Microenvironment

Substances

  • Biomarkers
  • CERS5 protein, human