A comprehensive analysis of the pyruvate kinase M1/2 (PKM) in human cancer.

Abstract

Background: Pyruvate Kinase Muscle Isozyme (PKM), as a member of the pyruvate kinase, is a key enzyme in glycolysis. Numerous tumors have demonstrated its oncogenic properties. There is, however, no pan-carcinogenic analysis for PKM.

Methods: A thorough analysis of PKM across various types of cancer was carried out using bioinformatics resources like The National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium (CPTAC) and The Cancer Genome Atlas (TCGA) database. This study involved analyzing the role of PKM in 33 various types of cancers, along with investigating gene expressions, survival rates, clinical importance, genetic changes, immune system presence, and related signaling pathways. Furthermore, we evaluated the effects of PKM knockdown on human colon carcinoma, and glioblastoma cell lines by in vitro experimentation.

Results: In most tumors, PKM expression was markedly increased and was associated with unfavorable overall survival (OS) in certain individuals. In addition, infiltration of macrophages was associated with PKM expression in various tumors. PKM was linked to glycolysis/gluconeogenesis, HIF-1 signaling, carbon metabolism, and NADPH regeneration in a mechanistic manner. Additionally, cell experiments showed that the knockdown of PKM could reduce the proliferation and migration abilities while promoting the apoptosis of Caco-2, and U-87 MG cells.

Conclusion: PKM controls immune cell infiltration, impacts patient outcomes in various types of cancer, and plays an essential role in proliferation and migration in some tumor cells by affecting glycometabolism. The PKM molecule may serve as a potential prognostic biomarker and therapeutic target for human cancers.