Pyruvate kinase M2 (PKM2) expression correlates with prognosis in solid cancers: a meta-analysis

Abstract

Pyruvate kinase M2 (PKM2) is the key enzyme in the Warburg effect and plays a central role in cancer cell metabolic reprogramming. Recently, quite a few studies have investigated the correlation between PKM2 expression and prognosis in multiple cancer patients, but results were inconsistent. We therefore performed a meta-analysis to explore the prognostic value of PKM2 expression in patients with solid cancer. Here twenty-seven individual studies from 25 publications with a total of 4796 cases were included to explore the association between PKM2 and overall survival (OS) or disease-free survival (DFS)/ progression-free survival (PFS)/ recurrent-free survival (RFS) in subjects with solid cancer. Pooled analysis showed that high levels of PKM2 was significantly associated with a poorer overall survival (HR = 1.73; 95%CI = 1.48-2.03) and DFS/ PFS/ RFS (HR = 1.90; 95%CI = 1.39-2.59) irrespective of cancer types. Different analysis models (univariate or multivariate models), sample-sizes (≤100 or >100), and methods for data collection (direct extraction or indirect extraction) had no impact on the negative prognostic effect of PKM2 over-expression. Nevertheless, stratified by cancer type, high-expression of PKM2 was associated with an unfavorable OS in breast cancer, esophageal squamous carcinoma, hepatocellular carcinoma and gallbladder cancer; whereas was not correlated with a worse OS in pancreatic cancer and gastric cancer. In conclusion, over-expression of PKM2 is associated with poor prognosis in most solid cancers and it might be a potentially useful biomarker for predicting cancer prognosis in future clinical applications.