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

Abstract

PurposeThe 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.MethodsA 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.ResultsWe 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.ConclusionOur 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.

Association Between Pretreatment Serum Apolipoprotein A1 and Prognosis of Solid Tumors in Chinese Population: A Systematic Review and Meta-Analysis

“…The synthesized data suggested that decreased level of serum apoA1 was significantly correlated with some phenotypes of tumor progression, such as larger tumor size, poor histological grade, and advanced clinical stage. All these aggressive tumor behaviors have been documented to be independent factors related to tumor progression and compromise survival outcome [49, 50]. Herein, apoA1 played an important role in the inhibition of tumor progression through different pathways.…”

“…The result was considered statistically significant if the 95% CI did not overlap 1. Heterogeneity was qualitatively examined through the chi-squared Q test and quantitatively estimated using the I 2 metric ( I 2 < 25%, no heterogeneity; I 2 = 25% – 50%, moderate heterogeneity; I 2 > 50%, extreme heterogeneity) [24]. When significant heterogeneity was observed ( P < 0.05 or I 2 > 50%), a random-effects model was used to calculate the pooled HR estimation.…”

Reprogramming of glucose metabolism in hepatocellular carcinoma: Progress and prospects

“…PKL and PKR are mainly expressed in liver cells and erythrocytes, respectively, whereas PKM1 is constitutively expressed in normal cells. The over-expression of PKM2 was frequently observed in malignances and predicts worse prognosis[31,32]. A recent study demonstrated that the expression of PKM2 is up-regulated in HCC and is a predictor of survival and recurrence[33].…”

Secreted Pyruvate Kinase M2 Promotes Lung Cancer Metastasis through Activating the Integrin Beta1/FAK Signaling Pathway

“…Additionally, PKM2 has been reported to function as a protein kinase to regulate gene transcription in nuclei (Jiang et al, 2014;Yang et al, 2012) and reprogram oxidative phosphorylation to aerobic glycolysis to promote tumor cell proliferation and migration in mitochondria . Overexpression of PKM2 has been universally found in human cancers and associated with poor clinical outcomes (Li et al, 2014a;Lim et al, 2012;Wu et al, 2016). Furthermore, PKM2 has been found in the extracellular fluid of patients with gastrointestinal cancer, pancreatic ductal adenocarcinoma, lung cancer, ovarian cancer, and renal cell carcinoma (Amin et al, 2019).…”