MCT4 has a potential to be used as a prognostic biomarker - a systematic review and meta-analysis

The role of several metabolic changes, such as hypoxia and acidosis, in the tumour environment has caught the attention of researchers in cancer progression and invasion. Lactate transport is one of the acidosis-enhancing processes that are mediated via monocarboxylate transporters (MCTs). We conducted a systematic review and meta-analysis to investigate the expression of two cancer-relevant MCTs (MCT1 and MCT4) and their potential prognostic significance in patients with metastasis of different types of cancer. Studies were included if they reported the number of metastatic tissue samples expressing either low or high levels of MCT1 and/or MCT4 or those revealing the hazard ratios (HRs) of the overall survival (OS) or disease-free survival (DFS) as prognostic indicators. During the period between 2010 and 2018, a total of 20 articles including 3831 patients (56.3% males) were identified. There was a significant association between MCT4 expression (high versus low) and lymph node metastasis [odds ratio (OR)=1.87, 95% confidence interval (CI)=1.10-3.17, P=0.02] and distant metastasis (OR=2.18, 95%CI=1.65-2.86, P<0.001) and the correlation remained significant for colorectal and hepatic cancer in subgroup analysis. For survival analysis, patients with shorter OS periods exhibited a higher MCT4 expression [hazard ratio (HR)=1.78, 95%CI=1.49-2.13, P<0.001], while DFS was shorter in patients with high MCT1 (HR=1.48, 95%CI=1.04-2.10, P=0.03) and MCT4 expression (HR=1.70, 95%CI=1.19-2.42, P=0.003) when compared to their counterparts with low expression levels. Future research studies should consider the pharmacologic inhibition of MCT4 to effectively inhibit cancer progression to metastasis.