Tissue expression of lactate transporters (MCT1 and MCT4) and prognosis of malignant pleural mesothelioma (brief report)

Our plain-English summary of Tissue expression of lactate transporters (MCT1 and MCT4) and prognosis of malignant pleural mesothelioma (brief report), by I. Dell'Anno, E. Barone, L. Mutti, et al (Journal of Translational Medicine, 2020).

The study

• Authors: I. Dell'Anno, E. Barone, L. Mutti, D.M. Rassl, S.J. Marciniak, R. Silvestri, S. Landi, F. Gemignani
• Journal: Journal of Translational Medicine
• Published: 2020;18(1):341
• Cited by: 21 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Malignant pleural mesothelioma (MPM) is an aggressive neoplasm of the pleura, mainly related to asbestos exposure. As in other solid tumors, malignant cells exhibit high glucose uptake and glycolytic rates with increased lactic acid efflux into the interstitial space. Lactate transport into and out of cells, crucial to maintaining intracellular pH homeostasis and glycolysis, is carried out by monocarboxylate transporters (MCTs) and the chaperone basigin (CD147). We set out to examine the clinical significance of basigin, MCT1 and MCT4 in the context of MPM and to evaluate their expression in relation to the evolution of the disease.

Methods: We used immunohistochemistry to measure the expression of basigin, MCT1 and MCT4 in a cohort of 135 individuals with MPM compared to a series of 15 non-MPM pleura specimens. Moreover, by Kaplan-Meier and Cox analyses we evaluated whether an expression over the average of these markers could be associated with the patients' overall survival (OS).

Results: We detected positive staining of basigin, MCT1, and MCT4 in most MPM specimens. In particular, MCT4 was always positive in malignant tissues but undetectable in the 4 normal pleural specimens incorporated within the tissue microarray. This was confirmed in the additional series of 15 normal pleural samples. Moreover, MCT4 expression was significantly associated with reduced OS.

Conclusion: In this study, the tissue expression of basigin did not prove to be exploitable as a diagnostic or prognostic marker for MPM patients. The expression of MCT1 was not informative either, being tightly correlated with that of basigin. However, the expression of MCT4 showed promise as a diagnostic/therapeutic and prognostic biomarker.

In plain English

This brief report studied archived tumour tissue from 135 patients with malignant pleural mesothelioma. The tissue came from MesobanK, and patients in the tissue collection had been diagnosed between 2005 and 2010. The study did not examine asbestos exposure. The authors stained the tissue for the lactate transporters MCT1 and MCT4 and for basigin, a helper protein that holds these transporters in place at the cell membrane. They then compared the staining with survival. Usable scores came from 88 to 90 patients. Patients with high MCT4 had shorter overall survival (hazard ratio 1.70, 95% confidence interval 1.09 to 2.70). When other factors were taken into account, the MCT4 result was borderline (hazard ratio 1.67, 95% confidence interval 0.99 to 2.81, P = 0.054). Basigin and MCT1 levels showed no statistically significant link with survival. Fifteen normal pleura samples from people who had surgery for recurrent pneumothorax were all reported negative for MCT4. Public data on 87 mesothelioma samples showed a similar survival pattern for the MCT4 gene. The authors proposed MCT4 as a possible prognostic marker and said its sensitivity and predictive value need further study.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory study of archived tumour tissue: immunohistochemistry on a tissue microarray, with survival analysis (Kaplan–Meier and Cox models); published as a brief report
• Who was studied: Diagnostic tissue from 135 patients with malignant pleural mesothelioma. The tissue came from MesobanK. Patients in the tissue microarray had been diagnosed with malignant mesothelioma between 2005 and 2010. Expression scores were obtained for 89 (basigin), 88 (MCT1) and 90 (MCT4) patients. Comparison tissue was 4 normal pleura samples in the microarray plus 15 normal pleura samples from people who had bullectomy and pleurectomy for recurrent pneumothorax.
• Exposure: Asbestos exposure was not studied. The factor studied was tissue expression of the lactate transporters MCT1 and MCT4 and of their chaperone protein basigin (CD147), each classified as low or high expression.
• Main results:
  • Among mesothelioma patients, high MCT4 expression was significantly associated with shorter overall survival (log-rank P = 0.019, HR = 1.70; 95% CI 1.09–2.70)
  • Overall survival at one, two and three years was 70%, 40% and 20% for patients with low MCT4, compared with 40%, 20% and 0% for patients with high MCT4
  • Among patients with epithelioid mesothelioma only (n = 68), the MCT4 association was weaker and not statistically significant (log-rank P = 0.053, HR = 1.69, 95% CI 0.99–2.88)
  • In the multivariate analysis (adjusting for age, gender, histological subtype, previous cancer, therapy and mesothelial markers), high MCT4 had HR 1.67 (95% CI 0.99–2.81), P = 0.054. In the same analysis, low calretinin expression and lack of therapeutic intervention were associated with statistically significant shorter survival.
  • No statistically significant association was found between overall survival and basigin or MCT1 levels
  • MCT1 expression was correlated with basigin expression (P less than 0.0001); MCT4 expression was not
  • All 15 non-neoplastic pleura samples were negative for MCT4 but positive for basigin and MCT1
  • In public TCGA data on 87 mesothelioma samples, low mRNA expression of the MCT4 gene (SLC16A3) was associated with longer survival. Median survival was 400 days with high expression and double that with low expression (log-rank P = 0.004, HR = 2.47, 95% CI 1.34–4.53).
• The authors' conclusion: The authors proposed that MCT4 tissue expression could serve as a novel prognostic biomarker for patients with malignant pleural mesothelioma and as a possible target for new inhibitors. They concluded that basigin and MCT1 expression were not useful as diagnostic or prognostic markers.
• Limitations the authors state:
  • The authors stated that the sensitivity and predictive value of MCT4 must be addressed in further studies before any clinical use
  • The authors stated that analyses by histological subtype had low statistical power
  • The authors stated that more healthy and malignant specimens are needed to confirm whether MCT4 could be used as a diagnostic marker

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Prognosis, Pleural Mesothelioma, Neoplasm, Pleura, Asbestos Exposure, Interstitial, Immunohistochemistry, Overall Survival.

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