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BACKGROUND: MCT4 is a lactate transporter associated with glycolysis, which has been found to be associated with various tumorigenesis and development processes. Gastric cancer is a malignant disease with high incidence and mortality. The role of MCT4 in the occurrence and development of gastric cancer has not been clarified. METHODS: In this study, we comprehensively utilized single-cell sequencing and external transcriptome sequencing databases to deeply analyze the mechanism of the impact of MCT4 on gastric cancer and its microenvironment. We verified the function of MCT4 in gastric cancer through in vitro cell line experiments and in vivo experiments using gastric cancer liver metastasis and subcutaneous tumor models. Meanwhile, we collected tumor and normal tissue samples from clinical gastric cancer patients and employed immunohistochemistry and multiplex immunofluorescence techniques to detect the expression and localization of relevant indicators, thereby validating the results of computer simulation analysis and providing a basis for revealing the internal relationship between MCT4 and gastric cancer. RESULTS: The expression of MCT4 is upregulated in gastric cancer patients, and the upregulation is more significant than that in patients with gastric cancer metastasis. MCT4 can mediate the proliferation and migration of gastric cancer cells in vitro. MCT4 can mediate the metastasis of gastric cancer cells in vivo. Multi-omics analysis showed that the expression of MCT4 was related to the composition of the immune microenvironment, and it could mediate the emergence of the inhibitory immune microenvironment. The results of immunofluorescence and immunohistochemistry proved the robustness of the multi-omics analysis. CONCLUSION: Our study found that MCT4 plays an important role in the occurrence and development of gastric cancer, which may mediate the occurrence of gastric cancer metastasis and shape the immunosuppressive tumor microenvironment.
Jiang et al. (Wed,) studied this question.