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

  • Min YuEmail author
  • Shengying Chen
  • Weifeng Hong
  • Yujun Gu
  • Bowen Huang
  • Ye Lin
  • Yu Zhou
  • Haosheng Jin
  • Yanying Deng
  • Lei Tu
  • Baohua HouEmail author
  • Zhixiang JianEmail author
Original Article – Clinical Oncology



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.


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).


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.


Prognostic markers Survival Cancer Glycolysis Systematic review Meta-analysis 



This study was supported by grants from the National Science Foundation of Guangdong Province, China (no. 2014A030310073), Guangdong Province Public interest research and capacity—building projects, China (no. 2014A020212448), Natural Science Foundation of Guangdong Province—Doctor Foundation (no. 2014A030310073), and Guangzhou Science and technology plan of scientific research projects, China (no. 201510010286).

Compliance with ethical standards

Conflict of interest

This study was funded by the above institutions and has received research grants from it. All authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants performed by any of the authors.

Supplementary material

432_2019_2847_MOESM1_ESM.tif (5.1 mb)
Supplemental Fig. 1A: Forest plot of hazard ratio (HR) for the association between HIF-1&#x03B1; and OS (A), DFS (B) (TIF 5223 KB)
432_2019_2847_MOESM2_ESM.tif (4.3 mb)
Supplemental Fig. 1B: Forest plot of hazard ratio (HR) for the association between HIF-1&#x03B1; and OS (A), DFS (B) (TIF 4388 KB)
432_2019_2847_MOESM3_ESM.tif (3.3 mb)
Supplemental Fig. 2: Forest plot of hazard ratio (HR) for the association between p53 and OS (TIF 3375 KB)
432_2019_2847_MOESM4_ESM.tif (1.3 mb)
Supplemental Fig. 3A: Begg’s funnel plot for the assessment of publication bias in the present study for HIF-1. (A) OS, (B) DFS (TIF 1351 KB)
432_2019_2847_MOESM5_ESM.tif (1.3 mb)
Supplemental Fig. 3B: Begg’s funnel plot for the assessment of publication bias in the present study for HIF-1. (A) OS, (B) DFS (TIF 1351 KB)
432_2019_2847_MOESM6_ESM.tif (1.3 mb)
Supplemental Fig. 4: Begg’s funnel plot for the assessment of publication bias in the present study for p53 (TIF 1351 KB)
432_2019_2847_MOESM7_ESM.doc (18 kb)
Supplementary material 1 (DOC 18 KB)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of General SurgeryGuangdong Provincial People’s Hospital, Guangdong Academy of Medical SciencesGuangzhouChina
  2. 2.The Second Clinical Medical CollegeGuangzhou Medical UniversityGuangzhouChina

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