Monocarboxylate transporters 1-4 in NSCLC: MCT1 is an independent prognostic marker for survival

PLoS One. 2014 Sep 16;9(9):e105038. doi: 10.1371/journal.pone.0105038. eCollection 2014.

Abstract

Introduction: Monocarboxylate transporters (MCTs) 1-4 are lactate transporters crucial for cancers cells adaption to upregulated glycolysis. Herein, we aimed to explore their prognostic impact on disease-specific survival (DSS) in both cancer and tumor stromal cells in NSCLC.

Methods: Tissue micro arrays (TMAs) were constructed, representing both cancer and stromal tumor tissue from 335 unselected patients diagnosed with stage I-IIIA NSCLC. Immunohistochemistry was used to evaluate the expression of MCT1-4.

Results: In univariate analyses; ↓ MCT1 (P = 0.021) and ↑ MCT4 (P = 0.027) expression in cancer cells, and ↑ MCT1 (P = 0.003), ↓ MCT2 (P = 0.006), ↓ MCT3 (P = 0.020) expression in stromal cells correlated significantly with a poor DSS. In multivariate analyses; ↓ MCT1 expression in cancer cells (HR: 1.9, CI 95%: 1.3-2.8, P = 0.001), ↓ MCT2 (HR: 2.4, CI 95%: 1.5-3.9, P<0.001), ↓ MCT3 (HR: 1.9, CI 95%: 1.1-3.5, P = 0.031) and ↑ MCT1 expression in stromal cells (HR: 1.7, CI 95%: 1.1-2.7, P = 0.016) were significant independent poor prognostic markers for DSS.

Conclusions: We provide novel information of MCT1 as a candidate marker for prognostic stratification in NSCLC. Interestingly, MCT1 shows diverging, independent prognostic impact in the cancer cell and stromal cell compartments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / mortality*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / surgery
  • Cell Line, Tumor
  • Female
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / mortality*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / surgery
  • Male
  • Middle Aged
  • Monocarboxylic Acid Transporters / genetics
  • Monocarboxylic Acid Transporters / metabolism*
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism*
  • Neoplasm Staging
  • Prognosis
  • Risk Factors
  • Stromal Cells / metabolism
  • Symporters / genetics
  • Symporters / metabolism*

Substances

  • Biomarkers, Tumor
  • Monocarboxylic Acid Transporters
  • Muscle Proteins
  • SLC16A3 protein, human
  • SLC16A4 protein, human
  • SLC16A7 protein, human
  • Symporters
  • monocarboxylate transport protein 1

Grants and funding

This work was funded by the University of Tromsø. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.