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中国癌症防治杂志

中国癌症防治杂志 ›› 2020, Vol. 12 ›› Issue (5): 566-571.doi: 10.3969/j.issn.1674-5671.2020.05.15

• 临床研究 • 上一篇    下一篇

基于生物信息学分析结直肠癌STIM1高频突变介导的免疫抵抗模式及其分子机制

  

  1. 广西医科大学附属肿瘤医院结直肠外科
  • 出版日期:2020-10-25 发布日期:2020-10-25
  • 通讯作者: 唐卫中 Ｅ-ｍａｉｌ：tangweizhong@gxmu.edu.cn
  • 基金资助:
    国家自然科学基金项目（81973533）；广西科技计划项目（桂科AD19245197）

A bioinformatics-based analysis of immune resistance modes mediated by high frequency mutation of STIM1 in colorectal cancer and related molecular mechanisms

  1. Department of Colorectal Surgery, Guangxi Medical University Cancer Hospital
  • Online:2020-10-25 Published:2020-10-25
  • Contact: TANG Weizhong E-mail：tangweizhong@gxmu.edu.cn

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摘要： 目的 探讨结直肠癌（colorectal cancer，CRC）基因突变频谱及其介导的CRC免疫抵抗的分子机制。方法 选择2019年1月至2020年1月广西医科大学附属肿瘤医院收治的CRC患者36例，采用新一代测序（NGS）技术检测组织和血液样本中的基因突变情况。对突变频谱进行分子网络事件描述，采用TIMER和CancerSEA数据库对核心分子进行免疫浸润和组织单细胞分布分析，用Reactome数据库对核心分子进行功能聚类分析，利用STRING数据库分析核心免疫抵抗事件网络。结果 组织和血液样本检测结果显示，基质相互作用分子1（stromal interaction molecule 1，STIM1）为筛选的高频突变基因（突变频率为97.2%）。免疫浸润和单细胞分布显示STIM1与RELA、JUN共同参与免疫反应，STIM1、RELA与JUN mRNA在结肠癌患者中的表达与CD4+T细胞的浸润水平显著相关（r=0.554，0.565，0.319，均P<0.05），且RELA、JUN均与STIM1呈正相关 （r=0.579，0.223，均P<0.05）。Kaplan-Meier分析结果显示，CD4+T细胞和巨噬细胞浸润水平越高，结肠癌患者生存预后越差。功能聚类分析显示，STIM1与适应性免疫系统、固有免疫系统、免疫系统中的细胞因子信号转导以及免疫反应蛋白类泛素化修饰相关，PPI网络分析显示，STIM1与RELA、JUN相关。结论  STIM1可能与RELA、JUN共同参与免疫抵抗网络形成，是CRC免疫抵抗中的重要调控因素及潜在的治疗靶点。

关键词: 结直肠癌, 免疫抵抗, STIM1, RELA, JUN, 分子机制

Abstract: Objective To investigate the gene mutation spectrum of colorectal cancer (CRC) and the mediated molecular mechanism of CRC immune resistance. Methods A total of 36 CRC patients admitted to Guangxi Medical University Cancer Hospital from January 2019 to January 2020 were selected. New generation sequencing(NGS) was used to detect the gene mutation spectra in tissue and blood samples. The mutation spectra were described by molecular network events, TIMER and CancerSEA database were used to analyze the immune infiltration and tissue single cell distribution of core molecules, Reactome database was used for functional clustering analysis of core molecules, and the STRING database was used to analyze the core immune resistance event network. Results The results of tissue and blood samples showed that stromal interaction molecule 1(STIM1) was the screened high frequency mutation gene (The mutation frequency was 97.2%). Immune infiltration and single cell distribution showed that STIM1, RELA and JUN were involved in immune response. The expressions of STIM1, RELA and JUN mRNA in colon cancer patients were significantly correlated with the infiltration level of CD4+ T cells(r=0.554, 0.565, 0.319; all P<0.05). Meanwhile, RELA and JUN were positively correlated with STIM1(r=0.579, 0.223；all P<0.05). Kaplan-Meier analysis indicated that the higher the infiltration levels of CD4+ T cells and macrophages are, the worse the survival prognosis of colorectal cancer patients is. Functional cluster analysis identified that STIM1 was related to adaptive immune system, innate immune system, cytokine signaling in the immune system and ubiquitination modification of immunoreactive proteins, while PPI network analysis showed that STIM1 was related to RELA and JUN. Conclusions STIM1 may join RELA and JUN to form an immune resistance network, and becomes an important regulatory factor and potential therapeutic target in CRC immune resistance.

Key words: Colorectal cancer, Immune resistance, STIM1, RELA, JUN, Molecular mechanism

中图分类号: 

  • R735.3+5