基于COSMIC数据库的结直肠转移性癌的体细胞突变基因变化的研究

Study on the changes of somatic mutation in colorectal metastatic cancer based on COSMIC database

目的利用癌症体细胞突变目录(COSMIC)数据库,筛选结直肠原发性癌和结直肠转移性癌两类癌组织之间的具有显著差异的体细胞基因突变,并分析其可能的功能及通路。方法从COSMIC数据库下载结直肠癌全外显子测序数据,在R 3.5.0环境下,利用卡方检验或Fisher确切概率法对结直肠原发性癌和结直肠转移性癌两类癌组织之间的差异体细胞突变基因进行挖掘,记录具有显著差异的体细胞突变基因并进行功能及通路富集分析,探索其可能生物学功能及通路。结果共发现120个具有显著差异的体细胞突变基因,包括RHEB、RP11-368J21.2、AGAP10等,对其进行GO和KEGG富集分析显示,这些显著性差异体细胞突变基因可能与如脱氢酶活性、还原酶活性、细胞周期停滞、代谢途径、PI3K-Akt信号通路、细胞周期、细胞粘附分子、癌症中的转录失调、铂类耐药性等功能及通路相关。结论挖掘结直肠原发性癌和结直肠转移性癌之间的显著差异体细胞突变基因可为研究结直肠癌的转移调控机制提供借鉴,显著差异体细胞突变基因可能作为结直肠癌转移诊断标志物或转移治疗靶点应用于临床。

Objective To screen the significant differences in somatic gene mutations between primary colorectal cancer and colorectal metastatic cancer using the Catalogue of Somatic Mutations In Cancer Catalog(COSMIC) Database and analyze its possible functions and pathways. Methods The colorectal cancer whole-exome sequencing data was downloaded from the COSMIC database. In the R3.5.0 environment, the chi-square test or Fisher′ exact test was used to analysis the primary colorectal cancer and colorectal metastatic cancer. The differences in somatic mutation genes were mined, and somatically mutated genes with signi?cant differences were recorded and functional and pathway enrichment analysis was performed to explore their possible biological functions and pathways. Results A total of 120 somatic mutations, including RHEB, RP11-368 J21.2, AGAP10, etc, were found. The GO and KEGG enrichment analysis showed that these significant differences in somatic mutations may be related to dehydrogenase activity, reductase activity, cell cycle arrest, metabolic pathway, PI3 K-Akt signaling pathway, cell cycle,cell adhesion molecules, transcriptional disorders in cancer, platinum resistance, and other functions and pathways. Conclusion The signi?cant difference in somatic mutation between primary colorectal cancer and colorectal metastatic cancer can provide a reference for studying the metastasis mechanism of colorectal cancer. Signi?cant differences in somatic mutations may be used as clinical diagnostic markers for metastatic colorectal cancer or as targets for metastasis therapy.