Comprehensive Pan-cancer Analysis Revealed CASP10 As a Promising Biomarker For Diverse Tumor Types.

Abstract

We aimed to explore the comprehensive cancer landscape of Caspase-10 (CASP10). CASP10, a member of the caspase family, is located at the human chromosome locus 2q33-34. Studies have suggested its potential role in the development of certain cancers. To evaluate CASP10 expression in normal and pan-cancer tissues, we integrated data from The Cancer Genome Atlas (TCGA), GEO, Human Protein Atlas (HPA), and UALCAN databases. The diagnostic and prognostic significance of CASP10 was analyzed using Receiver Operating Characteristic (ROC), Cox regression, and Kaplan-Meier analysis. Correlations of CASP10 with clinical parameters were assessed via the Wilcoxon test, Kruskal-Wallis test, and logistic regression analysis. Genomic variations were explored with cBioPortal, GSCALite database, and UALCAN databases. LinkedOmics database was used to detect the function of CASP10 in pan-cancer. Interactions between CASP10 and the Tumor Immune Microenvironment (TIME) were investigated using TISIDB, TIMER2, and TISCH databases. The GSCALite database was utilized to assess the sensitivity of CASP10 to small-molecule drugs. In addition, Western Blotting (WB) was employed to detect the expression of the CASP10 in our clinical Liver Hepatocellular Carcinoma (LIHC) and Stomach Adenocarcinoma (STAD) cohorts. The transcription and protein expression of CASP10 significantly differ across cancer types, marking it as a biomarker for diagnosis and prognosis. Its expression correlated with certain clinical characteristics such as histological types and Alpha-Fetoprotein (AFP) levels. CASP10 gene exhibited a 2% alteration frequency across pan-cancer patients, with significant SNV and CNV profiles, and decreased methylation levels. CASP10 was closely related to the Nuclear Factor-κappa B (NF-κB), TNF, cell cycle, and JAK-STAT signal pathways. CASP10 showed correlation with immune components in the tumor microenvironment, including lymphocytes, immune stimulators, immune inhibitors, MHC molecules, chemokines, receptors, and Cancer-Associated Fibroblasts (CAFs). Importantly, CASP10 could predict the sensitivity of diverse anti-cancer drugs. Finally, WB analysis validated the overexpression of CASP10 in LIHC and STAD tissues. Our comprehensive bioinformatic analysis reveal the function of CASP10 on the diagnosis, prognosis, and progression of diverse cancer types.