Pan-Cancer Analysis of the Oncogenic and Prognostic Role of PKM2: A Potential Target for Survival and Immunotherapy

Abstract

Background: No pan-cancer study has been conducted till date to explore the comprehensive oncogenic roles of pyruvate kinase M2 (PKM2).

Methods: TCGA, TIMER, GEPIA, UALCAN, STRING, and other databases were used to analyze the expression, prognostic roles, epigenetic variants, and possible oncogenic mechanisms of PKM2. Proteomic sequencing data and PRM were applied to validate.

Results: PKM2 showed higher expression in majority of cancers, the expression being significantly correlated with the clinical stage. Higher expression of PKM2 was associated with lower OS and DFS in several cancers, such as MESO and PAAD. In addition, the epigenetic variation of PKM2, including gene alteration, mutation type and sites, DNA methylation, and phosphorylation, showed diversity in different cancers. All four methods indicated that PKM2 is positively associated with the immune infiltration of tumor-associated fibroblasts, such as in THCA, GBM, and SARC. Further mechanistic exploration suggested that the ribosome pathway might play an essential role in the regulation of PKM2, and interestingly, four out of ten hub genes were found to be highly related to OS in several cancers. Finally, in thyroid cancer specimen, we validated the expression and potential mechanisms by proteomic sequencing and PRM validation.

Conclusion: In the majority of cancers, the higher expression of PKM2 was highly associated with poor prognosis. Further molecular mechanism exploration implied that PKM2 might serve as a potential target for cancer survival and immunotherapy by regulating the ribosome pathway.