Relationship between Monocarboxylate Transporter-4 Expression and Breast Cancer Clinicopathology and Subtype in Sanglah General Hospital, Denpasar, Indonesia
DOI:
https://doi.org/10.3889/oamjms.2022.6934Keywords:
Breast cancer, Monocarboxylate transporter-4, ClinicopathologyAbstract
BACKGROUND: Based on the global cancer observatory (GLOBOCAN) data, in 2018, there were 18.1 million new breast cancer cases. Breast cancer is the second-most common malignancy after lung cancer, which contributed to 11.6% of all new cancer cases in 2018. 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 functions in the transport of lactate from the cytoplasm to the intercellular fluid.
METHODS: 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 covariates (stage, grade, and subtype). Of the three variables that were 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 which increases the risk of progression of the cancer stage as well as the risk of developing a more malignant (non-luminal) subtype.
CONCLUSION: High MCT-4 expression was significantly associated with malignant subtypes, high histological-grade cancer, and an advanced breast cancer.Downloads
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References
International Agency for Research on Cancer. Cancer Fact Sheets: Breast Cancer Estimated Incidence, Mortality, and Prevalence Worldwide. Lyon, France: International Agency for Research on Cancer; 2012.
Dimmer KS, Friedrich B, Lang F. The low-affinity monocarboxylate transporter MCT4 is adapted to the export of lactate in highly glycolytic cells. Biochem J. 2000;350(1):219-27. PMid:10926847 DOI: https://doi.org/10.1042/bj3500219
Franziska B, Sébastien D, Charlene B, Weigelt B, Dankworth B, Griffiths B. et al. Functional screening identifies MCT4 as a key regulator of breast cancer cell metabolism and survival. J Pathol. 2015;237(2):152-65. https://doi.org/10.1002/path.4562 PMid:25965974
Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature. 2012;490(7418):61-70. https://doi.org/10.1038/nature11412 PMid:23000897 DOI: https://doi.org/10.1038/nature11412
Parker JS, Mullins M, Cheang MC, Leung S, Voduc D, Vickery T. et al. Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol. 2009;27(8):1160-7. https://doi.org/10.1200/JCO.2008.18.1370 PMid:19204204 DOI: https://doi.org/10.1200/JCO.2008.18.1370
Tennant DA, Duran RV, Gottlieb E. Targeting metabolic transformation for cancer therapy. Nat Rev Cancer. 2010;10(4):267-77. https://doi.org/10.1038/nrc2817 PMid:20300106 DOI: https://doi.org/10.1038/nrc2817
Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: The metabolic requirements of cell proliferation. Science. 2009;324(5930):1029-3. https://doi.org/10.1126/science.1160809 PMid:19460998 DOI: https://doi.org/10.1126/science.1160809
Ward PS, Thompson CB. Metabolic reprogramming: A cancer hallmark even Warburg did not anticipate. Cancer Cell. 2012;21(3):297-308. https://doi.org/10.1016/j.ccr.2012.02.014 PMid:22439925 DOI: https://doi.org/10.1016/j.ccr.2012.02.014
Han T, Kang D, Ji D, Wang X, Zhan W, Fu M, et al. How does cancer cell metabolism affect tumor migration and invasion? Cell Adh Migr. 2013;7(5):395-403. https://doi.org/10.4161/cam.26345 PMid:24131935 DOI: https://doi.org/10.4161/cam.26345
Baenke F, Dubuis S, Brault C, Weigelt B, Dankworth B, Griffiths B, et al. Functional screening identifies MCT4 as a key regulator of breast cancer cell metabolism and survival. J Pathol. 2015;237(2):152-65. https://doi.org/10.1002/path.4562 PMid:25965974 DOI: https://doi.org/10.1002/path.4562
Pinheiro C, Albergaria A, Paredes J, Sousa B, Dufloth R, Vieira D, et al. Monocarboxylate transporter 1 is up-regulated in basal-like breast carcinoma. Histopathology. 2010;56(7):860-7. hptts://doi.org/10.1111/j.1365-2559.2010.03560.x PMid:20636790 DOI: https://doi.org/10.1111/j.1365-2559.2010.03560.x
Todenhöfer T, Seiler R, Stewart C, Moskalev I, Gao J, Ladhar S et al Selective inhibition of the lactate transporter mct4 reduces growth of invasive bladder cancer. Mol Cancer Ther. 2018;17(12):2746-55. https://doi.org/10.1158/1535-7163.MCT-18-0107 PMid:30262589 DOI: https://doi.org/10.1158/1535-7163.MCT-18-0107
Long Y, Gao Z, Hu X, Xiang F, Wu Z, Zhang J, et al. Downregulation of MCT4 for lactate exchange promotes the cytotoxicity of NK cells in breast carcinoma. Cancer Med. 2018;7(9):4690-700. https://doi.org/10.1002/cam4.1713 PMid:30051648 DOI: https://doi.org/10.1002/cam4.1713
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Copyright (c) 2022 Gede Andry Nicolas, I Wayan Sudarsa, Putu Anda Tusta Adiputra, Desak Made Wihandani, I Gede Putu Supadmanaba (Author)
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