Prognostic role of glycolysis for cancer outcome: evidence from 86 studies.

OBJECTIVE: The abnormal expression of the key enzymes in glycolytic pathways, including glucose transporter-1, glucose transporter-3, hexokinase-II, lactate dehydrogenase 5, pyruvate kinase M2, glucose-6-phosphate dehydrogenase, transketolase-like protein 1 and pyruvate dehydrogenase kinase-1 was reported to be associated with poor prognosis of various cancers. However, the association remains controversial. The objective of this study was to investigate the prognostic significance of glycolysis-related proteins. MATERIALS AND METHODS: We searched MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, using Pubmed and Ovid as search engines and Google Scholar from inception to April 2017. Eighty-six studies with 12,002 patients were included in the study. RESULTS: Our pooled results identified that glycolysis-related proteins in cancers were associated with shorter overall survival of colorectal cancer (HR 2.33, 95% CI 1.38-3.93, P = 0.002), gastric cancer (HR 1.55, 95% CI 1.31-1.82, P < 0.001), cancer of gallbladder or bile duct (HR 2.16, 95% CI 1.70-2.75, P < 0.001), oral cancer (HR 2.07, 95% CI 1.32-3.25, P < 0.001), esophageal cancer (HR 1.66, 95% CI 1.25-2.21, P = 0.01), hepatocellular carcinoma (HR 2.04, 95% CI 1.64-2.54, P < 0.001), pancreatic cancer (HR 1.72, 95% CI 1.39-2.13, P < 0.001), breast cancer(HR 1.67, 95% CI 1.34-2.08, P < 0.001), and nasopharyngeal carcinoma (HR 3.59, 95% CI 1.75-7.36, P < 0.001). No association was found for lung cancer, ovarian cancer or melanoma. The key glycolytic transcriptional regulators (HIF-1α, p53) were analyzed in parallel to the glycolysis-related proteins, and the pooled results identified that high-level expression of HIF-1α was significantly associated with shorter overall survival (HR 0.57, 95% CI 0.42-0.79, P < 0.001) Furthermore, glycolysis-related proteins linked with poor differentiated tumors (OR 1.81, 95% CI 1.46-2.25, P < 0.001), positive lymph node metastasis (OR 2.73, 95% CI 2.16-3.46, P < 0.001), positive vascular invasion (OR 2.05, 95% CI 1.37-3.07, P < 0.001), large tumor size (OR 2.06, 95% CI 1.80-2.37, P < 0.001), advanced tumor stage (OR 1.58, 95% CI 1.19-2.09, P < 0.001), and deeper invasion (OR 2.37, 95% CI 1.93-2.91, P < 0.001). CONCLUSION: Glycolytic transcriptional regulators and glycolysis-related proteins in cancers were significantly associated with poor prognosis, suggesting glycolytic status may be potentially valuable prognostic biomarkers for various cancers.

The prognostic value of GLUT1 in cancers: a systematic review and meta-analysis.

Increased glycolysis is one of the hallmarks of cancer. The abnormal expression of glucose transporter 1 (GLUT1) was reported to be associated with resistance to current therapy and poor prognosis. Numerous studies have investigated the correlation between GLUT1 expression and prognosis in cancers, but the conclusions are still controversial. Here, we conducted a meta-analysis to explore the association between GLUT1 and survival in human cancers. PubMed, Springer, Medline, and Cochrane Library were searched carefully to identify eligible studies evaluating prognostic value of GLUT1 in cancers. Twenty-seven studies with 4079 patients were included in the present study. Our pooled results identified that increased expression of GLUT1 was associated with unfavorable overall survival (HR = 1.780, 95% CI = 1.574-.013, p < 0.001)) and poorer disease-free survival (HR = 1.95, 95% CI = 1.229-3.095, p = 0.003). Furthermore, overexpression of GLUT1 linked with poor differentiated tumors (RR = 1.380, 95% CI = 1.086-1.755, p = 0.009; I2 = 72.0%, p < 0.001), positive lymph node metastasis (RR = 1.395, 95% CI = 1.082-1.799, p = 0.010; I2 = 70.8%, p = 0.002) and larger tumor size (RR = 1.405, 95% CI = 1.231-1.603, p < 0.001; I2 = 37.3%, p = 0.093). This systematic review and meta-analysis indicated that the GLUT1 may serve as an ideal prognostic biomarker in various cancers.