MCT1在预测肝细胞癌患者预后中的作用研究

The role of MCT1 in predicting the prognosis of patients with hepatocellular carcinoma

目的:探讨乳酸转运载体单羧酸转运蛋白1(monocarboxylate transporter 1,MCT1)在肝细胞肝癌(hepatocellular carcinoma,HCC)患者预后预测中的应用价值及相应的调控机制。方法:筛选临床HCC患者行肝切除后的组织标本,通过比较与癌旁组织的表达差异区分MCT1高表达组与低表达组;研究不同组患者外周血免疫细胞分型与活化情况,以及肿瘤免疫浸润情况。回顾性分析43例HCC手术患者乳酸和MCT1高表达与低表达组的生存与复发差异。结果:MCT1高表达组与低表达组相比,外周血免疫细胞分型无明显差异,但CD4+T细胞更易在乳酸刺激下转化为Treg(调节型T)细胞;乳酸环境下,MCT1高表达组Treg细胞具有明显升高的代谢水平;病理标本分析发现MCT1高表达组具有较低的炎性细胞浸润和较高的免疫抑制因子转录水平(Foxp3、CTLA4、IL-10)。回顾较早手术患者分析后显示,肿瘤内乳酸表达水平与患者预后无明显相关性,而MCT1高表达组预后和复发水平明显差于MCT1低表达组。结论:MCT1表达水平对HCC患者具备很好的预测价值,MCT1-Treg相关通路可能作为新的肝癌诊断、治疗、预后评估靶点。

Objective:This study aims to explore the application value and possible mechanism of monocarboxy transporter 1(MCT1)in the prediction of prognosis for the patients with hepatocellular carcinoma(HCC).Methods:We selected the tissues of HCC patients after liver resection,and used RT-PCR to estimate the expression of MCT1 and divided the patients into MCT1 high and MCT1 low groups;the phenotype and activation of the immune cells from the peripheral blood as well as the immune statues of the resected liver tissues from both groups were analyzed.A retrospective analysis of the relationship between the overall survival(OS)and diseasefree survival(DFS)rate to the expression of lactate or MCT1 between 43 HCC patients who underwent liver surgery was also compared.Results:Although there was no difference in the phenotype of immune cells from peripheral blood,CD4+T cells were easier to transform into Treg cells under the stimulation of lactic acid in the high MCT1 expression group;under the environment of lactic acid,the Treg cells from the MCT1 high expression group presented a significant increase of metabolism level;MCT1 high expression group had lower immune cell infiltration and up-regulated expression of anti-inflammatory cytokines(Foxp3,CTLA3,IL-10).The OS and DFS rate were much worse in MCT1 high patients comparing with MCT1 low group.Conclusion:MCT1-Treg related targets may serve as a new target for the diagnosis,therapeutic and prognosis prediction of HCC.