Abstract
Progestin and adipoQ receptor family member 4 (PAQR4) is a protein-coding gene. Recent studies have shown that PAQR4 is related to the development of multiple cancers. However, there is no systematic pan-cancer analysis of this gene. In this study, the expression of PAQR4, correlations with clinical prognosis, immune situation, and its potential molecular functions and mechanisms in pan-cancer were explored by bioinformatics analysis. The Cancer Genome Atlas was applied to investigate the relations between PAQR4 and clinical features, prognostic effects, and tumor immune microenvironment. R software was used to perform statistical analysis and figure creation. The expression of PAQR4 in BLCA and KIRC was validated by qRT-PCR and immunohistochemistry, and its function was explored by cellular experiments. Bioinformatics analysis revealed that PAQR4 was up-regulated in multiple cancers and related to poor prognosis. The high expression of PAQR4 was closely associated with high tumor stage, immune cell infiltration, tumor mutation burden, and microsatellite instability in different cancer types. In addition, the high expression of PAQR4 also indicated involvement in the immune regulatory pathways. The involvement of PAQR4 in the immune regulation of different tumors was confirmed by GSEA enrichment analysis. Moreover, PAQR4 was highly expressed in bladder cancer and renal clear cell carcinoma tissues and cell lines. Cell proliferation, migration, and invasion of bladder cancer and renal clear cell carcinoma cell lines were significantly decreased after the knockdown of PAQR4. This study elucidated the role of PAQR4 in carcinogenesis as well as tumor immunity. PAQR4 may serve as a potential prognostic biomarker in a variety of cancers.