Abstract
BACKGROUND: Folate hydrolase-1 (FOLH1) is the gene encoding prostate-specific membrane antigen (PSMA) and is highly associated with prostate cancer. However, its involvement in other tumorigenesis remains to be investigated. This study aims to elucidate its role in multiple cancers through various bioinformatics approaches. METHODS: In this study, we integrated the multi-omics data of TCGA (The Cancer Genome Atlas Program), GTEx (The Genotype-Tissue Expression), and CPTAC (Clinical Proteomic Tumor Analysis Consortium) to analyze the expression pattern, genetic variation, copy number alteration (CNA), and methylation characteristics of FOLH1 in 33 cancers by using tools such as TIMER 2.0, GEPIA 3, and cBioPortal. We also assessed its prognostic significance by survival analysis and combined the immune infiltration algorithm with the drug sensitivity database to reveal its relationship with the tumor microenvironment, including immune checkpoints, tumor mutation burden (TMB), microsatellite instability (MSI), and chemotherapy response. RESULTS: FOLH1 expression was significantly up-regulated in uterine corpus endometrial carcinoma (UCEC), adrenocortical carcinoma (ACC), and colon adenocarcinoma (COAD), and low in breast invasive carcinoma (BRCA) and liver hepatocellular carcinoma (LIHC). Survival analysis showed that high FOLH1 expression was significantly associated with shorter overall survival (OS) in patients with ACC and pancreatic adenocarcinoma (PAAD), but showed the opposite trend in stomach adenocarcinoma (STAD). CONCLUSIONS: FOLH1 may be involved in tumor progression by regulating amino acid metabolic pathways and the immune microenvironment. It is a promising pan-cancer prognostic marker and synergistic target for immunotherapy.