2025 Volume 48 Issue 12 Pages 1960-1971
l-Lactate is not merely a metabolic product of glycolysis but also a molecule that plays an important role in intercellular interactions. Monocarboxylate transporters (MCTs) 1–4 are membrane proteins responsible for transporting monocarboxylic acids, such as l-lactate, across the plasma membrane. MCTs have been suggested to be involved in cancer cell invasion, metastasis, and immune evasion. Several studies have reported the relationship between MCT expression in tumor tissues and cancer prognosis. However, the potential for MCTs as poor prognostic factors in cancer remains controversial, and the impacts of different MCT isoforms and cancer types are yet to be fully elucidated. Therefore, we conducted a meta-analysis by pooling previously reported hazard ratios. The expression of MCT1 and MCT4, but not MCT2, in tumors and MCT4 in stromal cells was significantly associated with cancer prognosis. In addition, subgroup analyses revealed that both MCT1 and MCT4 expression were associated with esophageal cancer prognosis, whereas MCT4 expression was associated with hepatocellular carcinoma prognosis. Unlike MCT1, the plasma membrane expression of MCT4 was found to be associated with cancer prognosis. Put together, our findings show that MCT4 is a promising target for the treatment of various cancers. Further integration of basic and clinical research is required to elucidate the mechanisms by which MCTs contribute to poor cancer prognosis, in turn facilitating the development of effective inhibitors.
