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Review
. 2015:2015:242437.
doi: 10.1155/2015/242437. Epub 2015 Dec 8.

Prognostic Indications of Elevated MCT4 and CD147 across Cancer Types: A Meta-Analysis

Cory D Bovenzi  1 , James Hamilton  2 , Patrick Tassone  2 , Jennifer Johnson  3 , David M Cognetti  2 , Adam Luginbuhl  2 , William M Keane  2 , Tingting Zhan  4 , Madalina Tuluc  5 , Voichita Bar-Ad  6 , Ubaldo Martinez-Outschoorn  3 , Joseph M Curry  2
Affiliations
Review

Prognostic Indications of Elevated MCT4 and CD147 across Cancer Types: A Meta-Analysis

Cory D Bovenzi et al. Biomed Res Int. 2015.

Abstract

Background: Metabolism in the tumor microenvironment can play a critical role in tumorigenesis and tumor aggression. Metabolic coupling may occur between tumor compartments; this phenomenon can be prognostically significant and may be conserved across tumor types. Monocarboxylate transporters (MCTs) play an integral role in cellular metabolism via lactate transport and have been implicated in metabolic synergy in tumors. The transporters MCT1 and MCT4 are regulated via expression of their chaperone, CD147.

Methods: We conducted a meta-analysis of existing publications on the relationship between MCT1, MCT4, and CD147 expression and overall survival and disease-free survival in cancer, using hazard ratios derived via multivariate Cox regression analyses.

Results: Increased MCT4 expressions in the tumor microenvironment, cancer cells, or stromal cells were all associated with decreased overall survival and decreased disease-free survival (p < 0.001 for all analyses). Increased CD147 expression in cancer cells was associated with decreased overall survival and disease-free survival (p < 0.0001 for both analyses). Few studies were available on MCT1 expression; MCT1 expression was not clearly associated with overall or disease-free survival.

Conclusion: MCT4 and CD147 expression correlate with worse prognosis across many cancer types. These results warrant further investigation of these associations.

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Figures

Figure 1
Figure 1
Multicompartment metabolism model in cancer. Modified with permission from Curry et al. [6].
Figure 2
Figure 2
Elevated MCT4 expression is associated with decreased overall survival. (a) Elevated MCT4 expression in the tumor microenvironment is associated with decreased OS. (b) Elevated MCT4 expression in cancer cells is associated with decreased OS. (c) Elevated MCT4 expression in stromal cells is associated with decreased OS. SCC: squamous cell carcinoma.
Figure 3
Figure 3
Elevated MCT4 expression is associated with decreased disease-free survival. (a) Elevated MCT4 expression in the tumor microenvironment is associated with decreased DFS. (b) Elevated MCT4 expression in cancer cells is associated with decreased DFS. (c) Elevated MCT4 expression in stromal cells is associated with decreased DFS. HNSCC: head and neck squamous cell carcinoma; CA: carcinoma; and SCC: squamous cell carcinoma.
Figure 4
Figure 4
Elevated CD147 expression is associated with decreased survival. (a) Elevated CD147 expression in cancer cells is associated with decreased overall survival. (b) Elevated CD147 expression in cancer cells is associated with decreased disease-free survival. CA: carcinoma; TNBC: triple-negative breast cancer; SCC: squamous cell carcinoma; and NSCLC: non-small-cell lung cancer.
Figure 5
Figure 5
MCT1 expression in the tumor microenvironment is not associated with overall survival. NSCLC: non-small-cell lung cancer; SCLC: small-cell lung cancer.
See this image and copyright information in PMC

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