MCM10基因介导肿瘤免疫逃避及其对多种癌症免疫治疗反应预测价值

    MCM10 gene mediating tumor immune evasion and its predictive value for immunotherapy response in various cancers

    • 摘要:
      目的 探讨微染色体维持蛋白10(minichromosome maintenance 10,MCM10)在肿瘤微环境、疾病分期、预后和肿瘤治疗反应中的作用及机制。
      方法 采用Timer、UALCAN、GEPIA、GPS-Prot、GSCALite、TIDE algorithm、Protein Data Bank、STRING等数据库分析MCM10在肿瘤免疫浸润、免疫逃逸、肿瘤进展、治疗反应和不同类型癌症队列预后中的作用。
      结果 MCM10在几乎所有TCGA肿瘤类型和亚型中均有异常表达,并与肿瘤分期、转移和不良预后有关。MCM10在不同的癌症类型中通过不同的机制参与肿瘤免疫逃逸,在肾脏透明肾细胞癌、结肠癌和肝细胞癌中是通过T细胞排斥和肿瘤免疫细胞的浸润。MCM10的遗传改变和致癌特征与BEND7、SEPHS1、OPTN、UCMA、PHYH、CANK1D、CCDC3、PRPF18、SEC81A2、FAM107B、NUDT5、PROSER2、ECHDC3、CELF2、CDC123基因相关,这些基因参与了细胞周期和DNA复制。MCM10的表达与各种癌症的免疫治疗密切相关。同时发现,较高的MCM10表达水平与癌细胞对丝裂原活化蛋白激酶抑制剂的敏感性降低有关。此外,MCM10对免疫检查点阻断亚队列的应答结果和总体存活率比肿瘤基因突变负荷、T细胞克隆性和B细胞克隆性显示出更高的预测能力。
      结论 MCM10是一种免疫致癌分子,可以作为癌症检测、预后、治疗设计和随访的生物标志物。

       

      Abstract:
      Objective To investigate the role and mechanism of minichromosome maintenance 10 (MCM10) in tumor microenvironment, disease stage, prognosis and response to tumor therapy.
      Methods The role of MCM10 in tumor immune invasion, immune escape, tumor progression, treatment response and prognosis of different types of cancer cohorts were analyzed using the Timer, UALCAN, GEPIA, GPS-Prot, GSCALite, TIDE algorithm, Protein Data Bank and STRING databases.
      Results MCM10 was abnormally expressed in almost all TCGA tumor types and subtypes, and associated with tumor stage, metastasis, and poor prognosis. MCM10 was involved in tumor immune escape through different mechanisms in different cancer types, and renal clear renal cell carcinoma, colon cancer, and hepatocellular carcinoma through T cell rejection and tumor immune cell infiltration. The genetic alterations and oncogenic churacteristics of MCM10 were correlated with BEND7, SEPHS1, OPTN, UCMA, PHYH, CANK1D, CCDC3, PRPF18, SEC81A2, FAM107B, NUDT5, PROSER2, ECHDC3, CELF2 and CDC123 genes, which were involved in cell cycle regulation and DNA replication. The expression of MCM10 was closely related to immunotherapy of various cancers. It was also found that the high expression level of MCM10 was associated with the decreasing sensitivity of cancer cells to mitogen-activated protein kinase inhibitors. In addition, the MCM10 responses to immune checkpoint blocking subcohorts and overall survival showed greater predictive power than tumor mutation load, T cell clonality, and B cell clonality.
      Conclusions MCM10 is an immunooncogenic molecule that can serve as a biomarker for cancer detection, prognosis, treatment design and follow-up.

       

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