MCT1在预测肝细胞癌患者预后中的作用研究
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江苏省自然科学基金(BK0201486)


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

    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。

    Abstract:

    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 disease-free 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.

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韩 晟,周锦仁,邵 青,戴新征,古 鉴. MCT1在预测肝细胞癌患者预后中的作用研究[J].南京医科大学学报(自然科学版),2022,42(2):184-188

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  • 收稿日期:2021-11-30
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  • 在线发布日期: 2022-03-01
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