BERKELEY, CA (UroToday.com) - Prostate cancer (PCa) is still the most frequently diagnosed malignancy among Western men. The widespread utility of serum prostate-specific antigen (PSA) contributed to a considerable increase in PCa incidence, leading to an increase in prostate biopsies. This, in turn, resulted in the diagnosis of many tumors that not have become clinically significant during a patient’s lifetime. PSA screening remains the most common screening method for PCa, and thus, new reliable markers for prostate cancer are urgently needed.
The recent recognition of metabolic alterations as a hallmark of cancer highlights the importance of lactate transporters, namely monocarboxylate transporters (MCTs), responsible for the transport of lactate in and out of the cells according to their metabolic demands, which contribute to the maintenance of the metabolic phenotype of cancer cells. Many descriptions on the expression of MCTs, in various cancer types, have been published in recent years, showing that they are differentially expressed among tumours. They are also being explored as therapeutic targets, with promising results. However, their role in cancer is not fully understood.
Mainly isoforms 1 and 4 (MCT1, MCT4, respectively) have been associated with poor prognosis parameters in cancer in contrast to MCT2, which does not appear to play such a significant role in most tumours. However, it does appear to be important in prostate cancer and may fill the criteria of tumour biomarker. In the work recently published by our group, we demonstrated that there was upregulation of MCT2 in prostate cancer, which prompted us to further explore this isoform as a tumour biomarker. Thus, we showed that MCT2 expression was similar to the well-established prostate cancer biomarker AMACR, along progression to malignancy, and importantly, evaluation of MCT2 together with AMACR (as positive biomarkers) and the negative markers p63 or 34βE12 increases two very important parameters in the diagnosis field, which are positive and negative predictive value. However, as for AMACR, MCT2 did not show any association with poor prognosis parameters, suggesting that its expression should be more related to disease initiation and the maintenance of the slow-growing localized disease, with no major role in disease progression.
The main challenge in PCa diagnosis continues to be how to distinguish patients with low-risk PCa -- who will show slow progression of disease (candidates for active surveillance) -- from patients at risk of a more aggressive disease (candidates for additional treatment). In this way, we propose MCT2 as a putative prostate cancer biomarker possibly involved in the slow-growing cancer type. However, to fully understand the biological relevance of MCT2 overexpression in this type of tumour, further studies are needed. Importantly, our publications in prostate cancer[1, 2] also support the exploitation of the metabolic alterations occurring during prostate cancer progression as sources of diagnostic markers and therapeutic targets, relevant to the management of prostate cancer. We strongly believe that the definition of low-risk and high-risk PCa is somehow linked to tumour metabolic demands.
In summary, despite recent improvements in the identification and discovery of novel PCa biomarkers, we are still a long way away from using these markers in the clinical setting. We support the use of a biomarker combination panel to increase the diagnostic accuracy and better manage low-risk PCa protocols. In this way, MCT2 should be further explored to take major advantage of its specific and sensitive expression in malignant prostate glands.
- Pértega-Gomes N, Vizcaíno JR, Miranda-Gonçalves V, Pinheiro C, Silva J, Pereira H, Monteiro P, Henrique RM, Reis RM, Lopes C and Baltazar F. Monocarboxylate transporter 4 (MCT4) and CD147 overexpression is associated with poor prognosis in prostate cancer, BMC cancer, 2011; 11:312.
- Pértega-Gomes N; Vizcaíno JR; Gouveia C; Jerónimo C; Henrique RM; Lopes C; Baltazar F. "Monocarboxylate transporter 2 (MCT2) as a putative biomarker in prostate cancer." The Prostate, 2013;73(7):763-9. Epub 2012 Nov 28.
Nelma Pértega-Gomesa, b and Fátima Baltazara, b as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
aLife and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal
b2ICVS/3B’s - PT Government Associate Laboratory, Braga/Guimarães, Portugal