Pan-cancer analysis of G6PD carcinogenesis in human tumors

Abstract

Abstract Glucose-6-phosphate dehydrogenase (G6PD) is involved in the catalytic pentose phosphate pathway (PPP), which is closely related to energy metabolism. G6PD plays a crucial role in many types of cancer, but the specific molecular mechanisms of G6PD in cancer remain unclear. Therefore, we investigated the potential oncogenic role of G6PD in various tumors based on The Cancer Genome Atlas (TCGA), the cBioPortal datasets, the University of California Santa Cruz (UCSC) Xena browser, and the UALCAN-based online tool. G6PD was highly expressed in several cancer tissues (hepatocellular carcinoma, glioma, and breast cancer) compared with normal tissues and was significantly associated with poor prognosis of hepatocellular carcinoma, clear cell renal cell carcinoma, and breast cancer. Promoter methylation levels of G6PD were lower in Bladder Urothelial Carcinoma (BLCA) (P = 2.77e−02), breast invasive carcinoma (BRCA) (P = 1.62e−12), kidney renal clear cell carcinoma (KIRC) (P = 4.23e−02), kidney renal papillary cell carcinoma (KIRP) (P = 2.64e−03), liver hepatocellular carcinoma (LIHC) (P = 1.76e−02), stomach adenocarcinoma (STAD) (P = 3.50e−02), testicular germ cell tumors (TGCT) (P = 1.62e−12), higher in prostate adenocarcinoma (PRAD) (P = 1.81e−09), and uterine corpus endometrial carcinoma (UCEC) (P = 2.96e−04) compared with corresponding normal tissue samples. G6PD expression was positively correlated with the infiltration level of immune cells in most tumors, suggesting that G6PD may be involved in tumor immune infiltration. In addition, the functional mechanism of G6PD also involves ‘Carbon metabolism’, ‘Glycolysis/Gluconeogenesis’, ‘Pentose phosphate pathway’, and ‘Central carbon pathway metabolism in cancer signaling pathway’. This pan-cancer study provides a relatively broad understanding of the oncogenic role of G6PD in various tumors and presents a theoretical basis for the development of G6PD inhibitors as therapeutic drugs for multiple cancers.