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Relationship between Monocarboxylate Transporter 4 (MCT-4) Expression and Breast Cancer Clinicopathology and Subtype in Sanglah General Hospital, Denpasar, Indonesia

Abstract

Background: Breast cancer is the second leading cause of death in women in developing countries. The activity of Warburg and Reverse-Warburg effects on breast cancer is reflected by the expression patterns of two molecules, namely caveolin-1 and Monocarboxylate Transporter-4 (MCT-4). MCT-4 is a transmembrane transport protein that transports lactate from the cytoplasm to the intercellular fluid.

Method: This is a cross-sectional analytical study to determine the relationship between MCT-4 expression and breast cancer clinicopathology and subtypes. The study was conducted between April and May of 2020 with 62  breast cancer patients as samples in Sanglah General Hospital, Denpasar. Analysis was done with SPSS 25.

Results: A logistic regression analysis was performed to analyze the relationship between the dependent variable (MCT-4) and the covariates (stage, grade, and subtype). Of the three variables significantly associated with MCT-4 expression, only clinical-stage and subtype (luminal and non-luminal) remained independently associated with MCT-4 expression. Analysis on the clinical stage and subtype variables showed an adjusted OR of 4.727 (p = 0.047; 95% CI: 1.109 - 21.922) and 17.850 (p = 0.009; 95% CI: 2.069 - 154.003) , respectively. This suggests that MCT-4 has a significant association with subtype and clinical-stage, increasing the risk of cancer stage progression and developing a more malignant (non-luminal) subtype.

Conclusion: High MCT-4 expression was significantly associated with malignant subtypes, high histological-grade cancer and advanced breast cancer.

Section

References

  1. International Agency for Research on Cancer (IARC), (2012). Cancer Fact Sheets: Breast Cancer Estimated Incidence, Mortality, And Prevalence Worldwide In. 2012. GLOBOCAN.
  2. The Indonesian Health Ministry National Cancer Prevention Committee, (2016). Panduan Penatalaksanaan Kanker Payudara Jakarta, Indonesia.
  3. Axelson H, Fredlund E, Ovenberger M etal. Hypoxia-induced differentiation of tumor cells – a mechanism behind heterogeneity and aggressiveness of solid tumors. Semin Cell Dev Biol 2005; 16: 554 – 563.
  4. Baek G, Tse YF, Hu Z, et al. MCT4 defines a glycolytic subtype of pancreatic cancer with poor prognosis and unique metabolic dependencies. Cell Rep 2014; 9: 2233–2249.
  5. Cairns RA, Harris IS, Mak TW. Regulation of cancer cell metabolism. Nat Rev Cancer 2011; 11: 85–95.
  6. Brahimi-Horn MC, Bellot G, Pouyssegur J. Hypoxia and energetic tumour metabolism. Curr Opin Genet Dev 2011; 21: 67–72.
  7. Casciari JJ, Sotirchos SV, Sutherland RM. Variations in tumor cell growth rates and metabolism with oxygen concentration, glucose concentration, and extracellular pH. J Cell Physiol 1992; 151: 386 – 394.
  8. Curtis C, Shah SP, Chin SF, et al. The genomic and transcriptomic architecture of 2000 breast tumours reveals novel subgroups. Nature 2012; 486: 346–352.
  9. Dang, C. V., & Kim, J. W. Convergence of Cancer Metabolism and Immunity: an Overview. Biomolecules & Therapeutics, Biomol Ther (Seoul). 2018;26(1):4-9.
  10. Diaz-Ruiz R, Rigoulet M, Devin A. The Warburg and Crabtree effects: on the origin of cancer cell energy metabolism and of yeast glucose repression. Biochim Biophys Acta 2011; 1807: 568 – 576.
  11. Dimmer KS, Friedrich B, Lang F, et al. The low-affinity monocarboxylate transporter MCT4 is adapted to the export of lactate in highly glycolytic cells. Biochem J 2000; 350 (1): 219–227.
  12. Draoui N, Schicke O, Seront E, etal. Antitumor activity of 7-aminocarboxycoumarin derivatives, a new class of potent inhibitors of lactate influx but not efflux. Mol Cancer Ther 2014; 13: 1410 – 1418.
  13. Fantin VR, St-Pierre J, Leder P. Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance. Cancer Cell 2006; 9: 425–434.
  14. Franziska B., Sébastien D., Charlene B., et al. Functional screening identifies MCT4 as a key regulator of breast cancer cell metabolism and survival. J Pathol 2015; 237: 152–165.
  15. Galluzzi L, Kepp O, Vander Heiden MG, et al. Metabolic targets for cancer therapy. Nat Rev Drug Discov 2013; 12: 829–846.
  16. Grassian AR, Metallo CM, Coloff JL, et al. Erk regulation of pyruvate dehydrogenase flux through PDK4 modulates cell proliferation. Genes Dev 2011; 25: 1716–1733.
  17. Han, T., Kang, D., Ji, D., Wang, X., Zhan, W., Fu, M.,Wang, J. B. How does cancer cell metabolism affect tumor migration and invasion? Cell adhesion & migration, 2013:7(5): 395–403.
  18. Kan Z, Jaiswal BS, Stinson J, et al. Diverse somatic mutation patterns and pathway alterations in human cancers. Nature 2010; 466: 869 – 873.
  19. Lee GY, Kenny PA, Lee EH, et al. Three-dimensional culture models of normal and malignant breast epithelial cells. Nat Methods 2007; 4: 359–365.
  20. Lee I, Lee SJ, Kang WK, et al. Inhibition of monocarboxylate transporter 2 induces senescence-associated mitochondrial dysfunction and suppes progression of colorectal malignancies in vivo. Mol Cancer Ther 2012; 11: 2342–2351.
  21. LeFloch R, Chiche J, Marchiq I, et al. CD147subunitoflactate/H+ symporters MCT1 and hypoxia-inducible MCT4 is critical for energetics and growth of glycolytic tumors. Proc Natl Acad Sci USA 2011; 108: 16663–16668.

How to Cite

Nicolas, G. A. N. A., Sudarsa, I. W., Adiputra, P. A. T., Wihandani, D. M., & Supadmanaba, I. G. P. (2022). Relationship between Monocarboxylate Transporter 4 (MCT-4) Expression and Breast Cancer Clinicopathology and Subtype in Sanglah General Hospital, Denpasar, Indonesia. Intisari Sains Medis, 13(1), 30–34. https://doi.org/10.15562/ism.v13i1.1274

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Gede Andry Nicolas Andry Nicolas
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I Wayan Sudarsa
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Putu Anda Tusta Adiputra
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Desak Made Wihandani
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I Gede Putu Supadmanaba
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