Jiang Tao, Zhang Jingcheng, Zhao Sicheng, Zhang Mingsi, Wei Yunhai, Liu Xiaojuan, Zhang Shuo, Fan Wei, Liu Yueying, Lv Yuanlin, Zhang Guangji
School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.
Key Laboratory of Blood-Stasis-Toxin Syndrome of Zhejiang Province, Hangzhou, China.
J Transl Med. 2025 Mar 5;23(1):276. doi: 10.1186/s12967-025-06279-8.
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.
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.
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.
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.
MCT4是一种与糖酵解相关的乳酸转运蛋白，已发现其与多种肿瘤发生和发展过程相关。胃癌是一种发病率和死亡率都很高的恶性疾病。MCT4在胃癌发生发展中的作用尚未阐明。
在本研究中，我们综合利用单细胞测序和外部转录组测序数据库，深入分析MCT4对胃癌及其微环境影响的机制。我们通过体外细胞系实验以及使用胃癌肝转移和皮下肿瘤模型的体内实验，验证了MCT4在胃癌中的功能。同时，我们收集了临床胃癌患者的肿瘤和正常组织样本，并采用免疫组织化学和多重免疫荧光技术检测相关指标的表达和定位，从而验证计算机模拟分析的结果，并为揭示MCT4与胃癌之间的内在关系提供依据。
MCT4在胃癌患者中的表达上调，且这种上调在胃癌转移患者中更为显著。MCT4可在体外介导胃癌细胞的增殖和迁移。MCT4可在体内介导胃癌细胞的转移。多组学分析表明，MCT4的表达与免疫微环境的组成有关，并且它可以介导抑制性免疫微环境的出现。免疫荧光和免疫组织化学的结果证明了多组学分析的可靠性。
我们的研究发现，MCT4在胃癌的发生发展中起重要作用，它可能介导胃癌转移的发生并塑造免疫抑制性肿瘤微环境。
