Pyruvate kinase M2 overexpression and poor prognosis in solid tumors of digestive system: evidence from 16 cohort studies

PURPOSE The expression of pyruvate kinase M2 (PKM2) has been linked to tumor formation and invasion. Specifically, the relationship between high PKM2 expression and prognosis has been evaluated in solid tumors of digestive system. However, the prognostic value of PKM2 remains controversial. METHODS A literature search of PubMed, Embase, and Cochrane databases was conducted until October 2015. The end point focused on overall survival (OS). The pooled hazard ratio (HR) or odds ratio and the 95% confidence intervals were calculated to correlate PKM2 overexpression with OS and clinicopathological characteristics by employing fixed- or random-effects models, depending on the heterogeneity of the included studies. RESULTS We identified 18 cohorts in 16 studies involving 2,812 patients for this meta-analysis. Overall, the combined HR for OS in all tumor types was 1.74 (1.44-2.11; P<0.001). When stratified by tumor type, the influence of PKM2 expression on poor prognosis was also found in gastric cancer (HR =1.54 [1.08-2.21], P=0.018), esophageal squamous cell carcinoma (HR =1.71 [1.38-2.12], P<0.001), hepatocellular cancer (HR =1.92 [1.52-2.42], P<0.001), biliary cancer (HR =2.11 [1.50-2.95], P<0.001), and oral cancer (HR =3.49 [1.97-6.18], P<0.001), but not in pancreatic ductal adenocarcinoma (HR =1.03 [0.28-3.76], P=0.968). Furthermore, PKM2 overexpression had a negative effect on the late clinical stage of all tumor types except for pancreatic ductal adenocarcinoma. The high density of PKM2 overexpression was significantly associated with some clinical characteristics in different cancer types, such as tumor stage, modal metastasis, and tumor size. CONCLUSION Our findings revealed significant association of PKM2 overexpression with OS and certain clinicopathological features in solid tumors of digestive system, thereby suggesting that PKM2 might be an indicator of poor prognosis in digestive system cancers.