P4HA1 Acts as a Potential Target in Renal Cell Carcinoma and Pan-cancer

Abstract

Background: Prolyl 4-hydroxylase subunit alpha 1 (P4HA1) plays a vital role in providing the major part of the catalytic site of the active enzyme. Emerging evidence has revealed that P4HA1 participates in the initiation and development of several malignant tumors, nevertheless, the pan-analysis of P4HA1 remains unspecified. Methods: In this study, we carried out an in-depth analysis of the expression patterns and prognostic value of P4HA1 across the datasets of The Cancer Genome Atlas (TCGA ) and Kaplan-Meier Plotter. The genomic and epigenetic alterations, correlation with immune infiltration and DNA methylation of P4HA1 in different cancers were also analyzed across multiple databases. Moreover, we further explored the biological function and mechanism of P4HA1 in renal cell carcinoma (RCC). Results: The results characterized the different expression profile and prognostic values of P4HA1 in pan-cancer. Remarkably, P4HA1 expression was increased in kidney renal clear cell carcinoma (KIRC) and positively correlated with the OS and DFS of patients with kidney renal papillary cell carcinoma (KIRP). In addition, a positive correlation between P4HA1 expression and immune cell infiltration in KIRC was observed. We also identified a strong correlation between P4HA1 expression and immune checkpoint gene expression, microsatellite instability and tumor mutation burden in kidney chromophobe (KICH). Finally, the results of in vitro experiments verified that overexpression of P4HA1 promoted the proliferation, migration, invasion and the epithelial–mesenchymal transition (EMT) of RCC cells. Conclusion: Overall, our study suggested that P4HA1 might play a significant role in tumorigenesis and have the potential to be the target for the prognosis and therapy for several malignant tumors, especially for RCC.