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

  • Original Article – Clinical Oncology
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

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.

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Acknowledgements

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).

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  1. Min Yu, Shengying Chen, Weifeng Hong and Yujun Gu contributed equally to this work.

Authors and Affiliations

  1. Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China

    Min Yu, Shengying Chen, Bowen Huang, Ye Lin, Yu Zhou, Haosheng Jin, Yanying Deng, Lei Tu, Baohua Hou & Zhixiang Jian

  2. The Second Clinical Medical College, Guangzhou Medical University, Guangzhou, China

    Weifeng Hong & Yujun Gu

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  1. Min Yu
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Corresponding authors

Correspondence to Min Yu, Baohua Hou or Zhixiang Jian.

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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.

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

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432_2019_2847_MOESM1_ESM.tif

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

Supplemental Fig. 1B: Forest plot of hazard ratio (HR) for the association between HIF-1&#x03B1; and OS (A), DFS (B) (TIF 4388 KB)

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

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

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

Supplemental Fig. 4: Begg’s funnel plot for the assessment of publication bias in the present study for p53 (TIF 1351 KB)

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Yu, M., Chen, S., Hong, W. et al. Prognostic role of glycolysis for cancer outcome: evidence from 86 studies. J Cancer Res Clin Oncol 145, 967–999 (2019). https://doi.org/10.1007/s00432-019-02847-w

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