Prognostic significance of metabolic enzyme pyruvate kinase M2 in breast cancer: A meta-analysis

BACKGROUNDS: Numerous studies have reported that aberrant pyruvate kinase M2 isoform (PKM2) expressed in cancer, indicating that PKM2 plays a critical role in tumor initiation and progression. Nevertheless, its prognostic value in breast cancer tumor is yet contentious. Therefore, we performed this meta-analysis to evaluate the prognostic significance of PKM2 in breast cancer. METHODS: Eligible relevant literatures were retrieved by searching PubMed, the Cochrane Library, Embase through December 2016. Articles that comparing different PKM2 expression levels in human breast cancer tissues and prognostic significance were included. Software RevMan 5.3 and STATA (Review Manager (RevMan): [Computer program]. Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014. STATA: StataCorp. 2011. Stata Statistical Software: Release 12. College Station, TX: StataCorp LP) were applied to analyze the outcomes. Pooled results were presented in hazardous ratios (HRs) of 5-year overall survival (OS), progression-free survival (PFS), and odds ratios (ORs) of clinicopathological features with 95% confidence intervals. RESULTS: Data from 6 involved studies with 895 patients were summarized. Breast cancer patients with high PKM2 had a worse OS (pooled HR = 1.65, 95% CI = 1.31–2.08, P < .001) and PFS (pooled HR = 2.49, 95% CI = 1.84–3.36, P < .00001). High PKM2 expression is related to lymph node metastasis (N1+N2+N3 vs N0, OR = 1.97, 95%CI = 1.39–2.80, P = .0001). The outcome stability was verified via sensitivity analysis. But elevated PKM2 expression was not correlated to tumor stage (T2+T3 vs T1, pooled OR = 0.80, 95% CI = 0.36–1.77, P = .58) and differential grade (G2+G3 vs G1, OR = 2.74, 95%CI = 0.76–9.84, P = .12). No publication bias was found in the included studies for OS (Begg test, P = .260; Egger test, P = .747). CONCLUSIONS: High PKM2 expression denotes worse OS and PFS in breast cancer patients, and correlate with the lymph node metastasis. However, there is no evidence for the impact of PKM2 expression on T stage and tumor differentiation.