Skip to main content

Advertisement

SpringerLink
Log in

Glucose Transporter 1 Gene Variants Predict the Prognosis of Patients with Early-Stage Non-small Cell Lung Cancer

  • Translational Research and Biomarkers
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

This study was conducted to investigate whether polymorphisms of glucose transporter 1 (GLUT1) gene are associated with the prognosis of patients with non-small cell lung cancer (NSCLC) after surgical resection.

Methods

Five single nucleotide polymorphisms (SNPs) in GLUT1 were investigated in a total of 354 patients with NSCLC who underwent curative surgery. The association of the SNPs with patients’ survival was analyzed.

Results

Among the five SNPs investigated, two SNPs (GLUT1 rs3820589T > A and rs4658G > C) were significantly associated with OS in multivariate analyses. GLUT1 rs3820589T > A was associated with significantly better OS (adjusted hazard ratio [aHR] = 0.57, 95% confidence interval [CI] = 0.34–0.94, P = 0.03, under dominant model), and rs4658G > C was associated with significantly worse OS (aHR = 1.91, 95% CI = 1.09–3.33, P = 0.02, under recessive model). In the stratified analysis by tumor histology, the effect of these SNPs on OS was only significant in squamous cell carcinoma but not in adenocarcinoma. When the two SNPs were combined, OS decreased as the number of bad genotypes increased (Ptrend = 4 × 10−3).

Conclusions

This study suggests that genetic variation in GLUT1 may be useful in predicting survival of patients with early stage NSCLC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–74.

    Article  CAS  Google Scholar 

  2. Hsu PP, Sabatini DM. Cancer cell metabolism: Warburg and beyond. Cell. 2008;134:703–7.

    Article  CAS  Google Scholar 

  3. DeBerardinis RJ, Lum JJ, Hatzivassiliou G, et al. The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab. 2008;7:11–20.

    Article  CAS  Google Scholar 

  4. Riganti C, Gazzano E, Polimeni M, et al. The pentose phosphate pathway: an antioxidant defense and a crossroad in tumor cell fate. Free Rad Biol Med. 2012;53:421–36.

    Article  CAS  Google Scholar 

  5. Yeung SJ, Pan J, Lee MH. Roles of p53, MYC and HIF-1 in regulating glycolysis—the seventh hallmark of cancer. Cell Mol Life Sci. 2008;65:3981–99.

    Article  CAS  Google Scholar 

  6. Krzeslak A, Wojcik-Krowiranda K, Forma E, et al. Expression of GLUT1 and GLUT3 glucose transporters in endometrial and breast cancers. Pathol Oncol Res. 2012;18:721–8.

    Article  CAS  Google Scholar 

  7. Wachi S, Yoneda K, Wu R. Interactome-transcriptome analysis reveals the high centrality of genes differentially expressed in lung cancer tissues. Bioinformatics. 2005; 21:4205–8.

    Article  CAS  Google Scholar 

  8. Amann T, Maegdefrau U, Hartmann A, et al. GLUT1 expression is increased in hepatocellular carcinoma and promotes tumorigenesis. Am J Pathol. 2009;174:1544–52.

    Article  CAS  Google Scholar 

  9. Kawamura T, Kusakabe T, Sugino T, et al. Expression of glucose transporter-1 in human gastric carcinoma: association with tumor aggressiveness, metastasis, and patient survival. Cancer. 2001;92:634–41.

    Article  CAS  Google Scholar 

  10. Sawayama H, Ishimoto T, Watanabe M, et al. High expression of glucose transporter 1 on primary lesions of esophageal squamous cell carcinoma is associated with hematogenous recurrence. Ann Surg Oncol. 2014;21:1756–62.

    Article  Google Scholar 

  11. Ooi AT, Gower AC, Zhang KX, et al. Molecular profiling of premalignant lesions in lung squamous cell carcinomas identifies mechanisms involved in stepwise carcinogenesis. Cancer Prev Res. 2014;7:487–95.

    Article  CAS  Google Scholar 

  12. Osugi J, Yamaura T, Muto S, et al. Prognostic impact of the combination of glucose transporter 1 and ATP citrate lyase in node-negative patients with non-small lung cancer. Lung Cancer. 2015;88:310–8.

    Article  Google Scholar 

  13. Chen B, Tang H, Liu X, et al. miR-22 as a prognostic factor targets glucose transporter protein type 1 in breast cancer. Cancer Lett. 2015;356:410–7.

    Article  CAS  Google Scholar 

  14. Tohma T, Okazumi S, Makino H, et al. Overexpression of glucose transporter 1 in esophageal squamous cell carcinomas: a marker for poor prognosis. Dis Esophagus. 2005;18:185–9.

    Article  CAS  Google Scholar 

  15. Goos JA, de Cuba EM, Coupe VM, et al. Glucose transporter 1 (SLC2A1) and vascular endothelial growth factor A (VEGFA) predict survival after resection of colorectal cancer liver metastasis. Ann Surg. 2016;263:138–45.

    PubMed  Google Scholar 

  16. Kunkel M, Reichert TE, Benz P, et al. Overexpression of Glut-1 and increased glucose metabolism in tumors are associated with a poor prognosis in patients with oral squamous cell carcinoma. Cancer. 2003;97:1015–24.

    Article  CAS  Google Scholar 

  17. Starska K, Forma E, Jozwiak P, et al. Gene and protein expression of glucose transporter 1 and glucose transporter 3 in human laryngeal cancer-the relationship with regulatory hypoxia-inducible factor-1alpha expression, tumor invasiveness, and patient prognosis. Tumour Biol. 2015;36:2309–21.

    Article  CAS  Google Scholar 

  18. Shen YM, Arbman G, Olsson B, et al. Overexpression of GLUT1 in colorectal cancer is independently associated with poor prognosis. Int J Biol Markers. 2011;26:166–72.

    Article  CAS  Google Scholar 

  19. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66:7–30.

    Article  Google Scholar 

  20. Detterbeck FC, Boffa DJ, Tanoue LT. The new lung cancer staging system. Chest. 2009;136:260–71.

    Article  Google Scholar 

  21. Lee SY, Jin CC, Choi JE, et al. Genetic polymorphisms in glycolytic pathway are associated with the prognosis of patients with early stage non-small cell lung cancer. Sci Rep. 2016;6:35603.

    Article  CAS  Google Scholar 

  22. Meijer TW, Schuurbiers OC, Kaanders JH, et al. Differences in metabolism between adeno- and squamous cell non-small cell lung carcinomas: spatial distribution and prognostic value of GLUT1 and MCT4. Lung Cancer. 2012;76:316–23.

    Article  Google Scholar 

  23. Schuurbiers OC, Meijer TW, Kaanders JH, et al. Glucose metabolism in NSCLC is histology-specific and diverges the prognostic potential of 18FDG-PET for adenocarcinoma and squamous cell carcinoma. J Thorac Oncol. 2014;9:1485–93.

    Article  CAS  Google Scholar 

  24. Goodwin J, Neugent ML, Lee SY, et al. The distinct metabolic phenotype of lung squamous cell carcinoma defines selective vulnerability to glycolytic inhibition. Nature Commun. 2017;8:15503.

    Article  CAS  Google Scholar 

Download references

Acknowledgment

This study was supported in part by the National R&D Program for Cancer Control, Ministry of Health and Welfare, Republic of Korea (1720040), and in part by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (NRF-2016R1A1A1A05005315).

Disclosure

The authors declared that they have no conflict of interest.

Author information

Author notes

  1. Sook Kyung Do and Ji Yun Jeong have contributed equally to this work.

Authors and Affiliations

  1. Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea

    Sook Kyung Do MS, Jin Eun Choi PhD, Mi Jeong Hong PhD, Hyo-Gyoung Kang PhD & Jae Yong Park MD, PhD

  2. BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, Republic of Korea

    Sook Kyung Do MS & Jae Yong Park MD, PhD

  3. Department of Pathology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea

    Ji Yun Jeong MD

  4. Lung Cancer Center, Kyungpook National University Chilgok Hospital, Daegu, Republic of Korea

    Shin Yup Lee MD, PhD, Yangki Seok MD, PhD, Eung Bae Lee MD, PhD, Seung Soo Yoo MD, PhD & Jae Yong Park MD, PhD

  5. Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea

    Shin Yup Lee MD, PhD, Seung Soo Yoo MD, PhD, Jaehee Lee MD, PhD, Seung Ick Cha MD, PhD, Chang Ho Kim MD, PhD & Jae Yong Park MD, PhD

  6. Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Republic of Korea

    Jin Eun Choi PhD, Mi Jeong Hong PhD, Hyo-Gyoung Kang PhD & Jae Yong Park MD, PhD

  7. Medical Research Collaboration Center in Kyungpook National University Hospital and School of Medicine, Kyungpook National University, Daegu, Republic of Korea

    Won Kee Lee PhD

  8. Department of Thoracic Surgery, School of Medicine, Kyungpook National University, Daegu, Republic of Korea

    Yangki Seok MD, PhD & Eung Bae Lee MD, PhD

  9. Department of Radiology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea

    Kyung Min Shin MD

  10. Department of Biological Sciences, The University of Texas at Dallas, Richardson, TX, USA

    Michael L. Neugent MS & Jung-whan Kim DVM, PhD

  11. Yale School of Medicine, New Haven, CT, USA

    Justin Goodwin MS

  12. Yale Graduate School of Arts and Sciences, New Haven, CT, USA

    Justin Goodwin MS

Authors
  1. Sook Kyung Do MS
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ji Yun Jeong MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shin Yup Lee MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jin Eun Choi PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mi Jeong Hong PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hyo-Gyoung Kang PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Won Kee Lee PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yangki Seok MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Eung Bae Lee MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Kyung Min Shin MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Seung Soo Yoo MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Jaehee Lee MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Seung Ick Cha MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Chang Ho Kim MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Michael L. Neugent MS
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Justin Goodwin MS
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Jung-whan Kim DVM, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Jae Yong Park MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Shin Yup Lee MD, PhD or Jae Yong Park MD, PhD.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Do, S.K., Jeong, J.Y., Lee, S.Y. et al. Glucose Transporter 1 Gene Variants Predict the Prognosis of Patients with Early-Stage Non-small Cell Lung Cancer. Ann Surg Oncol 25, 3396–3403 (2018). https://doi.org/10.1245/s10434-018-6677-1

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-018-6677-1

Keywords

Search

Navigation