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  • 汤 绚,江慧洪,汤二将,等.比较基因组杂交技术分析结直肠癌远处转移的遗传变异[J].同济大学学报(医学版),2020,41(1):26-32.    [点击复制]
  • TANG Xuan,JIANG Hui-hong,TANG Er-jiang,et al.Comparative genomic hybridization analysis of genetic variation in distant metastasis of colorectal cancer[J].同济大学学报(医学版),2020,41(1):26-32.   [点击复制]
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比较基因组杂交技术分析结直肠癌远处转移的遗传变异
汤绚,江慧洪,汤二将,李华光,陈颖,林谋斌
0
(同济大学医学院,上海 200092; 同济大学附属杨浦医院普外科,上海 200090;同济大学医学院胃肠外科和转化医学研究所,上海 200090)
摘要:
目的 应用微阵列比较基因组杂交技术分析结直肠癌远处转移的遗传变异。方法 收集47例结直肠癌患者(发生/未发生远处转移=18/29)的临床数据以及新鲜组织标本,进行微阵列比较基因组杂交分析,筛选出与远处转移相关的基因组改变。进行功能富集分析和蛋白质-蛋白质相互作用(protein-protein interaction, PPI)网络分析,探索结直肠癌远处转移的分子机制。结果 47例肠癌标本都存在广泛的遗传变异。研究发现,218个DNA拷贝数改变与结直肠癌的远处转移相关,且它们主要位于17q、22q、12p。功能富集分析显示这些基因组改变与免疫反应、Wnt信号通路、同源染色体重组、趋化因子信号通路和MAPK信号通路等密切相关。通过PPI网络分析获得了39个关键基因,包括TP53、EP300、MDM2、BRCA1、MAPK1等。结论 与结直肠癌远处转移相关的遗传变异主要位于17q、22q、12p,其基因组改变与免疫反应、Wnt信号通路、MAPK信号通路等密切有关。
关键词:  结直肠癌  远处转移  比较基因组杂交  功能富集分析  DNA拷贝数改变
DOI:10.16118/j.1008-0392.2020.01.005
投稿时间:2019-08-19
基金项目:国家自然科学基金(81874201);上海市卫生和计划生育委员会项目(201840359);上海市科学技术委员会项目(19411971500)
Comparative genomic hybridization analysis of genetic variation in distant metastasis of colorectal cancer
TANG Xuan,JIANG Hui-hong,TANG Er-jiang,LI Hua-guang,CHEN Ying,LIN Mou-bin
(Tongji University School of Medicine, Shanghai 200092, China; Dept. of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai 200090, China;Institute of Gastrointestinal Surgery and Translational Medicine, Tongji University School of Medicine, Shanghai 200090, China)
Abstract:
Objective To analyze the genetic variation in distant metastasis of colorectal cancer by using microarray comparative genomic hybridization(CGH). Methods An array-based comparative genomic hybridization analysis was performed in 47 fresh colorectal cancer samples(18 cases in metastasis group and 29 cases in none-metastasis group) to examine the genomic alterations associated with distant metastasis. Functional enrichment analysis and protein-protein interaction(PPI) network analysis were conducted to explore the potential molecular mechanisms of distant metastasis. Results Extensive genetic variation was found in all 47 samples of colorectal cancer. There were 218 of DNA copy number alterations(DCNAs) associated with distant metastasis of colorectal cancer, which were mainly located at chromosomes 17q, 22q, and 12p. The functional enrichment analysis showed that these genomic alterations were closely correlated with immune response, Wnt pathway, homologous recombination, chemokine signaling pathway and MAPK signaling pathway. With PPI network analysis, 39 key genes including TP53, EP300, MDM2, BRCA1 and MAPK1 were found. Conclusion The study shows that genetic variations associated with distant metastasis of colorectal cancer are mainly located at chromosomes 17q, 22q, and 12p, which are closely correlated with immune response, Wnt pathway, MAPK signaling pathway and so on.
Key words:  colorectal cancer  distant metastasis  comparative genome hybridization  functional enrichment analysis  DNA copy number alterations

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