Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Clinical Research
  • Published:

GLUT1 expression in high-risk prostate cancer: correlation with 18F-FDG-PET/CT and clinical outcome

Prostate Cancer and Prostatic Diseases volume 23, pages 441–448 (2020)Cite this article

Subjects

Abstract

Background

Tumour 18F-FDG-uptake is of prognostic value in high-risk and metastatic prostate cancer (PCa). The aim of this study is to investigate the underlying glucose metabolism mechanisms of 18F-FDG-uptake on PET/CT imaging in PCa.

Methods

Retrospective analysis was conducted for 94 patients diagnosed with a Gleason sum ≥8 adenocarcinoma of the prostate at biopsy between July 2011 and July 2014 who underwent 18F-FDG-PET/CT imaging before radical prostatectomy (RP). 18F-FDG-uptake in primary lesion was measured by a blinded reader using maximum standardised uptake value (SUVmax). GLUT1, GLUT12 and HK2 expression were blindly scored after immunohistochemistry on specimens RP by three pathologists. Correlations between GLUT1, GLUT12 and HK2, and SUVmax were assessed using Spearman’s rank correlation test. Survival probabilities were based on the Kaplan–Meier method.

Results

With a median follow-up of 4.5 years, 56% (n = 53) of patients had biochemical recurrence (BCR), 7% (n = 7) progressed to castration-resistant prostate cancer (CRPC) disease, 13% (n = 12) developed metastasis and 6% (n = 6) died. Correlation was found between GLUT1 expression and SUVmax level (r = 0.25, p = 0.02). In addition, SUVmax was significantly higher in tumours with high GLUT1 expression (n = 17, 5.74 ± 1.67) than tumours with low GLUT1 expression (n = 71, 2.68 ± 0.31, p = 0.004). Moreover, a significant association was found between GLUT1 expression levels and SUVmax level (p = 0.005), lymph node status (p = 0.05), volume of cancer (p = 0.01), CRPC disease progression (p = 0.02) and metastasis development (p = 0.04). No significant difference between GLUT12 and HEX2 expression and SUVmax have been found.

Conclusions

GLUT1 expression in PCa tumours correlates with 18F-FDG-uptake and poor prognostic factors. These results suggest that this transporter is involved in the molecular mechanism of 18F-FDG-uptake in high-risk PCa and raise interest in targeting metabolic dependencies of PCa cells as a selective anticancer strategy.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: 18F-FDG PET/CT transaxial images and immunohistochemistry expression levels of GLUT1, GLUT2 and HK2 in high grade prostate cancer.
Fig. 2: Correlation between GLUT1, GLUT12 and HK2 with SUVmax.
Fig. 3: Kaplan-Meier curves of survival according to GLUT1 expression level.

Similar content being viewed by others

References

  1. Pavlova NN, Thompson CB. The emerging hallmarks of cancer metabolism. Cell Metab 2016;23:27–47.

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Cutruzzola F, Giardina G, Marani M, Macone A, Paiardini A, Rinaldo S, et al. Glucose metabolism in the progression of prostate cancer. Front Physiol. 2017;8:97.

    PubMed  PubMed Central  Google Scholar 

  3. Gonzalez-Menendez P, Hevia D, Mayo JC, Sainz RM. The dark side of glucose transporters in prostate cancer: Are they a new feature to characterize carcinomas? Int J Cancer. 2018;142:2414–24.

    CAS  PubMed  Google Scholar 

  4. Vaz CV, Marques R, Alves MG, Oliveira PF, Cavaco JE, Maia CJ, et al. Androgens enhance the glycolytic metabolism and lactate export in prostate cancer cells by modulating the expression of GLUT1, GLUT3, PFK, LDH and MCT4 genes. J cancer Res Clin Oncol. 2016;142:5–16.

    CAS  PubMed  Google Scholar 

  5. Yu M, Yongzhi H, Chen S, Luo X, Lin Y, Zhou Y, et al. The prognostic value of GLUT1 in cancers: a systematic review and meta-analysis. Oncotarget 2017;8:43356–67.

    PubMed  PubMed Central  Google Scholar 

  6. Wang J, Ye C, Chen C, Xiong H, Xie B, Zhou J, et al. Glucose transporter GLUT1 expression and clinical outcome in solid tumors: a systematic review and meta-analysis. Oncotarget 2017;8:16875–86.

    PubMed  PubMed Central  Google Scholar 

  7. Wang L, Xiong H, Wu F, Zhang Y, Wang J, Zhao L, et al. Hexokinase 2-mediated Warburg effect is required for PTEN- and p53-deficiency-driven prostate cancer growth. Cell Rep. 2014;8:1461–74.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. White MA, Tsouko E, Lin C, Rajapakshe K, Spencer JM, Wilkenfeld SR, et al. GLUT12 promotes prostate cancer cell growth and is regulated by androgens and CaMKK2 signaling. Endocr-Relat cancer. 2018;25:453–69.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Gonzalez-Menendez P, Hevia D, Alonso-Arias R, Alvarez-Artime A, Rodriguez-Garcia A, Kinet S, et al. GLUT1 protects prostate cancer cells from glucose deprivation-induced oxidative stress. Redox Biol 2018;17:112–27.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Xiao H, Wang J, Yan W, Cui Y, Chen Z, Gao X, et al. GLUT1 regulates cell glycolysis and proliferation in prostate cancer. Prostate 2018;78:86–94.

    CAS  PubMed  Google Scholar 

  11. Le A, Cooper CR, Gouw AM, Dinavahi R, Maitra A, Deck LM, et al. Inhibition of lactate dehydrogenase A induces oxidative stress and inhibits tumor progression. Proc Natl Acad Sci USA. 2010;107:2037–42.

    CAS  PubMed  Google Scholar 

  12. Chan DA, Sutphin PD, Nguyen P, Turcotte S, Lai EW, Banh A, et al. Targeting GLUT1 and the Warburg effect in renal cell carcinoma by chemical synthetic lethality. Sci Transl Med. 2011;3:94ra70.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Wolf A, Agnihotri S, Micallef J, Mukherjee J, Sabha N, Cairns R, et al. Hexokinase 2 is a key mediator of aerobic glycolysis and promotes tumor growth in human glioblastoma multiforme. J Exp Med. 2011;208:313–26.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Liu Y, Cao Y, Zhang W, Bergmeier S, Qian Y, Akbar H, et al. A small-molecule inhibitor of glucose transporter 1 downregulates glycolysis, induces cell-cycle arrest, and inhibits cancer cell growth in vitro and in vivo. Mol cancer therapeutics. 2012;11:1672–82.

    CAS  Google Scholar 

  15. Ooi AT, Gomperts BN. Molecular pathways: targeting cellular energy metabolism in cancer via inhibition of SLC2A1 and LDHA. Clin Cancer Res. 2015;21:2440–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Rani R, Kumar V. Recent update on human lactate dehydrogenase enzyme 5 (hLDH5) inhibitors: a promising approach for cancer chemotherapy. J medicinal Chem. 2016;59:487–96.

    CAS  Google Scholar 

  17. Vander Heiden MG. Targeting cancer metabolism: a therapeutic window opens. Nat Rev Drug Disco. 2011;10:671–84.

    Google Scholar 

  18. Martinez-Outschoorn UE, Peiris-Pages M, Pestell RG, Sotgia F, Lisanti MP. Cancer metabolism: a therapeutic perspective. Nat Rev Clin Oncol. 2017;14:113.

    PubMed  Google Scholar 

  19. Jadvar H. FDG PET in prostate cancer. PET Clin. 2009;4:155–61.

    PubMed  PubMed Central  Google Scholar 

  20. Eidelman E, Twum-Ampofo J, Ansari J, Siddiqui MM. The metabolic phenotype of prostate cancer. Front Oncol. 2017;7:131.

    PubMed  PubMed Central  Google Scholar 

  21. Chang CH, Wu HC, Tsai JJ, Shen YY, Changlai SP, Kao A. Detecting metastatic pelvic lymph nodes by 18F-2-deoxyglucose positron emission tomography in patients with prostate-specific antigen relapse after treatment for localized prostate cancer. Urologia internationalis 2003;70:311–5.

    PubMed  Google Scholar 

  22. Jadvar H, Desai B, Ji L, Conti PS, Dorff TB, Groshen SG, et al. Baseline 18F-FDG PET/CT parameters as imaging biomarkers of overall survival in castrate-resistant metastatic prostate cancer. J Nucl Med: Off Publ, Soc Nucl Med. 2013;54:1195–201.

    CAS  Google Scholar 

  23. Jadvar H, Velez E, Desai B, Ji L, Colletti PM, Quinn DI. Prediction of time to hormonal treatment failure in metastatic castrate-sensitive prostate cancer with (18)F-FDG PET/CT. J Nucl Med. 2019;60:1524–30.

  24. Beauregard JM, Blouin AC, Fradet V, Caron A, Fradet Y, Lemay C, et al. FDG-PET/CT for pre-operative staging and prognostic stratification of patients with high-grade prostate cancer at biopsy. Cancer Imaging 2015;15:2.

    PubMed  PubMed Central  Google Scholar 

  25. Lavallee E, Bergeron M, Buteau FA, Blouin AC, Duchesnay N, Dujardin T, et al. Increased prostate cancer glucose metabolism detected by (18)F-fluorodeoxyglucose Positron emission tomography/computed tomography in localised gleason 8-10 prostate cancers identifies very high-risk patients for early recurrence and resistance to castration. Eur Urol Focus. 2018;5:998–1006.

  26. Sun HW, Yu XJ, Wu WC, Chen J, Shi M, Zheng L, et al. GLUT1 and ASCT2 as predictors for prognosis of hepatocellular carcinoma. PLoS ONE 2016;11:e0168907.

    PubMed  PubMed Central  Google Scholar 

  27. Koh YW, Lee SJ, Park SY. Differential expression and prognostic significance of GLUT1 according to histologic type of non-small-cell lung cancer and its association with volume-dependent parameters. Lung Cancer 2017;104:31–7.

    PubMed  Google Scholar 

  28. Blayney JK, Cairns L, Li G, McCabe N, Stevenson L, Peters CJ, et al. Glucose transporter 1 expression as a marker of prognosis in oesophageal adenocarcinoma. Oncotarget 2018;9:18518–28.

    PubMed  PubMed Central  Google Scholar 

  29. Stewart GD, Gray K, Pennington CJ, Edwards DR, Riddick AC, Ross JA, et al. Analysis of hypoxia-associated gene expression in prostate cancer: lysyl oxidase and glucose transporter-1 expression correlate with Gleason score. Oncol Rep. 2008;20:1561–7.

    CAS  PubMed  Google Scholar 

  30. Vaz CV, Alves MG, Marques R, Moreira PI, Oliveira PF, Maia CJ, et al. Androgen-responsive and nonresponsive prostate cancer cells present a distinct glycolytic metabolism profile. Int J Biochem Cell Biol. 2012;44:2077–84.

    CAS  PubMed  Google Scholar 

  31. Meirelles GS, Schoder H, Ravizzini GC, Gonen M, Fox JJ, Humm J, et al. Prognostic value of baseline [18F] fluorodeoxyglucose positron emission tomography and 99mTc-MDP bone scan in progressing metastatic prostate cancer. Clin Cancer Res. 2010;16:6093–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Jadvar H. Prostate cancer: PET with 18F-FDG, 18F- or 11C-acetate, and 18F- or 11C-choline. J Nucl Med. 2011;52:81–9.

    PubMed  Google Scholar 

  33. Conteduca V, Oromendia C, Eng KW, Bareja R, Sigouros M, Molina A, et al. Clinical features of neuroendocrine prostate cancer. Eur J Cancer. 2019;121:7–18.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Liu Y. FDG PET-CT demonstration of metastatic neuroendocrine tumor of prostate. World J Surg Oncol. 2008;6:64.

    PubMed  PubMed Central  Google Scholar 

  35. Spratt DE, Gavane S, Tarlinton L, Fareedy SB, Doran MG, Zelefsky MJ, et al. Utility of FDG-PET in clinical neuroendocrine prostate cancer. Prostate 2014;74:1153–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Parida GK, Tripathy S, Datta Gupta S, Singhal A, Kumar R, Bal C, et al. Adenocarcinoma prostate with neuroendocrine differentiation: potential utility of 18F-FDG PET/CT and 68Ga-DOTANOC PET/CT Over 68Ga-PSMA PET/CT. Clin Nucl Med. 2018;43:248–9.

    PubMed  Google Scholar 

  37. Ma Y, Wang W, Idowu MO, Oh U, Wang XY, Temkin SM, et al. Ovarian cancer relies on glucose transporter 1 to fuel glycolysis and growth: anti-tumor activity of BAY-876. Cancers. 2018;11.pii: E33.

  38. Wood TE, Dalili S, Simpson CD, Hurren R, Mao X, Saiz FS, et al. A novel inhibitor of glucose uptake sensitizes cells to FAS-induced cell death. Mol cancer therapeutics. 2008;7:3546–55.

    CAS  Google Scholar 

  39. Deep G, Kumar R, Nambiar DK, Jain AK, Ramteke AM, Serkova NJ, et al. Silibinin inhibits hypoxia-induced HIF-1alpha-mediated signaling, angiogenesis and lipogenesis in prostate cancer cells: In vitro evidence and in vivo functional imaging and metabolomics. Mol carcinogenesis 2017;56:833–48.

    CAS  Google Scholar 

  40. Peng Y, Xing SN, Tang HY, Wang CD, Yi FP, Liu GL, et al. Influence of glucose transporter 1 activity inhibition on neuroblastoma in vitro. Gene 2019;689:11–7.

    CAS  PubMed  Google Scholar 

  41. Cao X, Fang L, Gibbs S, Huang Y, Dai Z, Wen P, et al. Glucose uptake inhibitor sensitizes cancer cells to daunorubicin and overcomes drug resistance in hypoxia. Cancer Chemother Pharmacol. 2007;59:495–505.

    CAS  PubMed  Google Scholar 

  42. Wang YD, Li SJ, Liao JX. Inhibition of glucose transporter 1 (GLUT1) chemosensitized head and neck cancer cells to cisplatin. Technol cancer Res Treat. 2013;12:525–35.

    PubMed  Google Scholar 

  43. Diaz R, Nguewa PA, Redrado M, Manrique I, Calvo A. Sunitinib reduces tumor hypoxia and angiogenesis, and radiosensitizes prostate cancer stem-like cells. Prostate 2015;75:1137–49.

    CAS  PubMed  Google Scholar 

  44. Suzuki S, Okada M, Takeda H, Kuramoto K, Sanomachi T, Togashi K, et al. Involvement of GLUT1-mediated glucose transport and metabolism in gefitinib resistance of non-small-cell lung cancer cells. Oncotarget 2018;9:32667–79.

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank David Simonyan for his kind assistance with data statistics.

Author information

Author notes

  1. These authors contributed equally: Salma Meziou, Cassandra Ringuette Goulet

Authors and Affiliations

  1. Urology Division, CHU de Québec Research Center, Québec, QC, Canada

    Salma Meziou, Cassandra Ringuette Goulet, Hélène Hovington, Étienne Lavallée, Michelle Bergeron, Hervé Brisson, Audrey Champagne, Bertrand Neveu, Didier Lacombe, Jean-Mathieu Beauregard & Frédéric Pouliot

  2. Department of Surgery, Faculty of Medicine, Laval University, Québec, QC, Canada

    Salma Meziou, Cassandra Ringuette Goulet, Hélène Hovington, Étienne Lavallée, Michelle Bergeron, Hervé Brisson, Audrey Champagne, Bertrand Neveu, Didier Lacombe, Jean-Mathieu Beauregard & Frédéric Pouliot

  3. Department of Pathology, CHU de Québec, Québec, QC, Canada

    Salma Meziou, Véronique Lefebvre & Julie Riopel

  4. Department of Radiology and Nuclear Medicine, Faculty of Medicine, Laval University, Québec, QC, Canada

    Jean-Mathieu Beauregard & François-Alexandre Buteau

  5. Department of Medical Imaging, CHU de Québec, Québec, QC, Canada

    Jean-Mathieu Beauregard & François-Alexandre Buteau

Authors
  1. Salma Meziou
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cassandra Ringuette Goulet
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hélène Hovington
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Véronique Lefebvre
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Étienne Lavallée
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Michelle Bergeron
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hervé Brisson
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Audrey Champagne
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Bertrand Neveu
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Didier Lacombe
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Jean-Mathieu Beauregard
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. François-Alexandre Buteau
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Julie Riopel
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Frédéric Pouliot
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

SM, HH, JR and FP designed the study. EL and MB revised patient’s data. HH, DL and HB performed the IHC. SM, VL and JR interpreted IHC slides. CRG and AC performed statistical analysis. JMB and FAB analysed PET/CT images. CRG build the figures and wrote the first draft of the manuscript. SM, HH, AC, BN and FP edit and revised the paper. FP supervised the study.

Corresponding author

Correspondence to Frédéric Pouliot.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Meziou, S., Ringuette Goulet, C., Hovington, H. et al. GLUT1 expression in high-risk prostate cancer: correlation with 18F-FDG-PET/CT and clinical outcome. Prostate Cancer Prostatic Dis 23, 441–448 (2020). https://doi.org/10.1038/s41391-020-0202-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41391-020-0202-x

This article is cited by

Search

Advanced search

Quick links