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.

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“…Studies graded with more than five scores were classified as high quality trials in methodology [45]. …”

The multifaceted role of autophagy in cancer and the microenvironment

“…Of note, pyruvate kinase (PKM2) is the final enzyme in the glycolytic pathway that controls the glycolytic flux and is therefore important for preventing accumulation of glycolytic intermediates . In cancer, PKM2 breakdown via CMA is increased, whereby reduced PKM2 associates with an accumulation of glycolytic intermediates that are rerouted toward branching biosynthetic pathways to support cancer growth . Likewise, the rate‐limiting enzyme hexokinase 2 (HK2) of the glycolytic pathway, was found to be selectively broken down via autophagy in liver cancer .…”

p16 and its putative interplay with metabolic factors in prostate cancer: An analysis based on public TCGA data

“…Metabolic cellular reprogramming represents a key event in cancer cells, and p16 seems to be involved in the metabolic switch to glycolysis during tumorigenesis, also regulating NADPH Oxidase 4 (NOX4) expression in pancreatic ductal adenocarcinoma (13). Pyruvate Kinase type M2 (PKM2) also plays a central role in cancer, modulating glucose metabolism to support malignant cell proliferation (14). PKM2 expression has been in fact shown to be associated with tumour progression in several studies (15)(16)(17)(18)(19); however, its involvement in prostate cancer remains to be fully elucidated (20).…”