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中华结直肠疾病电子杂志 ›› 2019, Vol. 08 ›› Issue (05) : 454 -460. doi: 10.3877/cma.j.issn.2095-3224.2019.05.004

所属专题: 文献

论著

基于癌症基因组图谱的结肠癌预后相关突变基因群的挖掘与分析
康争春1, 鄂继福1,(), 徐晓东1, 王颢1, 于恩达1,()   
  1. 1. 200433 上海,海军军医大学附属长海医院肛肠外科
  • 收稿日期:2018-09-14 出版日期:2019-10-25
  • 通信作者: 鄂继福, 于恩达
  • 基金资助:
    国家重点基础研究发展计划973计划(No.2015CB554001); 国家自然科学基金青年科学基金项目(No.81802434); 第二军医大学精准医学转化应用研究专项项目(No.2017JZ19)

Mining and analysis of prognosis-related mutant gene groups in colon cancer based on The Cancer Genome Atlas

Zhengchun Kang1, Jifu E1,(), Xiaodong Xu1, Hao Wang1, Enda Yu1,()   

  1. 1. Department of Colorectal Surgery, Changhai Hospital, PLA Navy Medical Uneversity, Shanghai 200433, China
  • Received:2018-09-14 Published:2019-10-25
  • Corresponding author: Jifu E, Enda Yu
  • About author:
    Corresponding author: E Jifu, Email:
    Yu Enda, Email:
引用本文:

康争春, 鄂继福, 徐晓东, 王颢, 于恩达. 基于癌症基因组图谱的结肠癌预后相关突变基因群的挖掘与分析[J/OL]. 中华结直肠疾病电子杂志, 2019, 08(05): 454-460.

Zhengchun Kang, Jifu E, Xiaodong Xu, Hao Wang, Enda Yu. Mining and analysis of prognosis-related mutant gene groups in colon cancer based on The Cancer Genome Atlas[J/OL]. Chinese Journal of Colorectal Diseases(Electronic Edition), 2019, 08(05): 454-460.

目的

利用癌症基因组图谱(TCGA)数据库,筛选结肠癌显著差异表达进而显著影响结肠癌患者预后的基因突变群。

方法

从TCGA数据库下载结肠癌单核苷酸突变数据和表达谱数据,在R 3.5.0环境下,利用wilcoxon秩和检验法筛选单核苷酸突变后表达显著差异的基因,利用survival程序包筛选单核苷酸突变后显著影响生存预后的基因,最后将两者结果取交集,为突变后表达水平有显著性差异合并生存率有显著差异的基因。对该基因群进行瀑布图可视化,分析其主要突变类型、突变影响、突变和临床病理因素相关性。

结果

共发现42个差异具有统计学意义的基因,包括MBD6,BCR,ZNF407,ZC3H18等,主要突变类型为错义突变,部分突变基因和TNM分期、性别相关。

结论

挖掘结肠癌显著差异表达合并生存率显著差异的突变基因,有助于帮助我们深入理解结肠癌发生、发展过程中的关键基因突变群,从而从整体上把控基因突变群对结肠癌发生、发展、转归的影响,并为将来的调控机制研究提供参考,有可能作为结肠癌预后标志物和治疗靶点应用于临床。

Objective

The Cancer Genome Atlas (TCGA) database was used to screen for gene mutations that significantly differentiated colon cancer and significantly affected the prognosis of colon cancer patients.

Methods

The colon cancer single nucleotide mutation data and expression profile data were downloaded from the TCGA database, and the genes with significant differences after single nucleotide mutations were screened by the Wilcoxon rank sum test in the R 3.5.0 environment, and the survival package was used to screen for genes that significantly affected survival prognosis after single nucleotide mutations. Finally, the results were taken as the intersection, and there were significant differences in the expression levels after mutation, and the genes with significant differences in survival rate. The gene map was visualized by waterfall plots to analyze the main mutation types, mutation effects, mutations and clinical pathological factors.

Results

A total of 42 genes with statistically significant differences were found, including MBD6, BCR, ZNF407, ZC3H18, etc. The main mutation types were missense mutations, and some of the mutations were related to TNM staging and gender.

Conclusions

Excavating a significant difference in the expression of colon cancer with a significant difference in the survival rate of the mutant gene helps us to understand the key gene mutations in the development and progression of colon cancer. Therefore, the influence of gene mutation group on the occurrence, development and outcome of colon cancer is grasped, and it provides a reference for future research on the regulation mechanism. It may be used as a prognostic marker and therapeutic target for colon cancer.

图1 突变数量前10位基因瀑布图
表1 突变数量前10位基因基本信息
图2 MBD6突变与mRNA表达、患者预后的相关性示意图。图2A:MBD6的野生型、突变型与mRNA表达水平的相关性,MBD6突变后其表达水平显著降低,P=0.002;图2B:MBD6野生型、突变型患者的总生存期生存曲线图,突变型患者生存期显著缩短,P=0.017
图3 BCR突变与mRNA表达、患者预后的相关性示意图。图3A:BCR的野生型、突变型与mRNA表达水平的相关性,BCR突变后其表达水平显著升高,P=0.001;图3B:BCR野生型、突变型患者的总生存期生存曲线图,突变型患者生存期显著缩短,P=0.028
图4 MBD6(rs762648935位点)表达情况
表2 突变型和野生型显著差异表达及生存曲线有显著差异的突变数量前10位基因基本信息
图5 突变型和野生型显著差异表达及生存曲线有显著差异的突变基因瀑布图
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