Glucose-6-phosphate Dehydrogenase (G6PD): the Role in Tumor Progression and Immunotherapy

Abstract Background: Numerous studies have shown that glucose-6-phosphate dehydrogenase (G6PD) is a tumor-promoting factor in a variety of malignancies. However, it is not entirely clear the role and the potential molecular mechanism of G6PDH in the pathogenesis or clinical prognosis of different tumors. Methods: This study first investigated the pan-tumoral expression of G6PD, then G6PD gene expression were studied in cancers, survival prognosis, tumor immunity, immunosuppressive cell infiltration, DNA methylation, gene alteration assay, and response to immunotherapy. We also investigated the function of G6PD in the development and prognosis of various cancers. Results: Our results suggest that G6PD expression was higher in tumor tissues than in normal tissues and was related to tumor stage, metastasis, and prognosis in most cancers and subtypes of the Cancer Genome Atlas. High G6PD expression is protective in a small number of cancers, including paraganglioma, pheochromocytoma, and ovarian serous cystadenocarcinoma. However, it is a risk factor for the majority of cancers. The prognosis for progression-free survival was better in people with G6PD alterations than in those without them. G6PD and immune cell infiltration were significantly positively correlated in prostate cancer, pancreatic adenocarcinoma, liver cancer, and low-grade glioma of the brain. Additionally, the degree of G6PD methylation was shown to inversely correlate with mRNA expression. The PGD, GCLM, SRXN1, TRIM16L, and TXNRD1 genes all showed significant positive correlation with G6PD expression level. The major genetic alterations were missense mutations in G6PD, and mutations at the R192C/S locus were detected in cutaneous melanoma, uterine cancer, and thyroid carcinoma. In several malignancies, G6PD expression is associated with immunological and chemotherapeutic outcomes. Conclusions: According to the study, patients who expressed more G6PD generally had better therapeutic outcomes. Our study highlights the role of G6PD in oncogenesis, detection, prognosis, and treatment planning.