Pan-Cancer Analysis of P3H1 and Experimental Validation in Renal Clear Cell Carcinoma

Abstract

Prolyl 3-hydroxylase 1 (P3H1) has been implicated in cancer development, but no pan-cancer analysis has been conducted on P3H1. In this study, for the first time, aspects associated with P3H1, such as the mRNA expression, any mutation, promoter methylation, and prognostic significance, the relationship between P3H1 and clinicopathological parameters, drug sensitivity, and immune cell infiltration were investigated by searching several databases including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), cBioPortal, and The Tumor Immune Evaluation Resource (TIMER2.0) using bioinformatics tools. The findings indicate significant differential expression of P3H1 in most tumors when compared to normal tissues, with a strong association with clinical prognosis. A pan-cancer Cox regression analysis revealed that high P3H1 expression is significantly associated with low overall survival in patients with brain lower grade glioma, kidney clear cell carcinoma, adrenocortical cancer, liver hepatocellular carcinoma, mesothelioma, sarcoma, uveal melanoma, bladder urothelial carcinoma, kidney papillary cell carcinoma, kidney chromophobe, thymoma, and thyroid carcinoma. A negative correlation was observed between P3H1 DNA methylation and its expression. P3H1 is significantly associated with infiltrating cells, immune-related genes, tumor mutation burden, microsatellite instability, and mismatch repair. Finally, A significant correlation was found between P3H1 expression and sensitivity to nine drugs. Thus, enhanced P3H1 expression is associated with poor prognosis in a variety of tumors, which may be due to its role in tumor immune regulation and tumor microenvironment. This pan-cancer analysis provides insight into the function of P3H1 in tumorigenesis of different cancers and provides a theoretical basis for further in-depth studies to follow.

Keywords: Immune infiltration; P3H1; Pan-cancer; Prognosis; Tumor microenvironment.