Prognostic Implication and Oncogenic Role of PNPO in Pan-Cancer

Objective: Pyridoxine 5'-phosphate oxidase (PNPO) is a key enzyme in the metabolism of vitamin B6 and affects the tumorigenesis of ovarian and breast cancers. However, the roles of PNPO in other types of cancer remain unknown. Methods: The expression of PNPO was interpreted by The Cancer Genome Atlas (TCGA) database and Genotype Tissue-Expression (GTEX) database. Analysis of PNPO genomic alterations and protein expression in human organic tissues was analyzed by the cBioPortal database and human multiple organ tissue arrays. PNPO with drug sensitivity analysis was performed from the CellMiner database. The correlations between PNPO expression and survival outcomes, clinical features, DNA mismatch repair system (MMR), microsatellite instability (MSI), tumor mutation burden (TMB), and immune-associated cell infiltration were analyzed using the TCGA, ESTIMATE algorithm, and TIMER databases. Gene Set Enrichment Analysis (GSEA) was applied to elucidate the biological function of PNPO in pan-cancer. Results: The differential analysis showed that the level of PNPO mRNA expression was upregulated in 21 tumor types compared with normal tissues, which was consistent with its protein expression in most cancer types. The abnormal expression of PNPO could predict the survival outcome of patients with esophageal carcinoma (ESCA), kidney renal clear cell carcinoma (KIRC), prostate adenocarcinoma (PRAD), ovarian serous cystadenocarcinoma (OV), and uveal melanoma (UVM). Furthermore, the most frequent mutation type of PNPO genomic was amplified. Moreover, the aberrant PNPO expression was related to MMR, MSI, TMB, and drug sensitivity in various types of cancer. The expression of PNPO was related to the infiltration levels of various immune-associated cells in pan-cancer by ESTIMATE algorithm and TIMER database mining. Conclusion: Our results suggest that PNPO is a potential molecular biomarker for predicting patient prognosis, drug sensitivity, and immunoreaction in pan-cancer.