基于生物信息学途径探究卵巢上皮性癌ctDNA体细胞突变

Bioinformatics based study of ctDNA somatic mutations in epithelial carcinoma of ovary

目的:通过探索卵巢上皮性癌的体细胞变异情况,为寻找卵巢上皮性癌ctDNA的诊治靶标提供线索。方法:从癌症基因组图谱(TCGA)数据库获取卵巢上皮性癌患者体细胞突变数据、基因转录组数据,利用R软件maftools包对数据进行体细胞突变分析、突变特征分析、超突变分析、信号通路富集分析及体细胞突变基因协同和互斥分析。结果:纳入卵巢上皮性癌体细胞突变数据下载样本共411例,其中突变种类最多的为错义突变;变体类型中SNP占比最大;SNV中T>G转换最多,T>A次之;突变频率最高的基因为TP53。SNP转换与颠倒比例相当,6种转换以C>T所占百分比最高(35.19%)。富集通路分析:RTK-RAS、Hippo信号通路有突变的样本占比分别为190/411和147/411。对TOP50基因的互作关系进行分析提示绝大部分基因是共同发生(协同性)。结论:本研究借助于TCGA数据库,完成了卵巢上皮性癌体细胞突变分析,为卵巢上皮性癌发生机制研究提供了一些参考与借鉴,为促进对癌症病因学的理解及研究ctDNA提供依据。

Objective:To explore the somatic variation of ovarian cancer,to provide clues for the diagnosis and treatment of ovarian cancer ctDNA targets.Methods:Somatic mutation data and gene transcriptome data of ovarian cancer patients were obtained from cancer Genome Atlas(TCGA)database.R software maftools package was used for somatic mutation analysis,mutation characteristics analysis,hypermutation analysis,signal pathway enrichment analysis and somatic mutation gene cooperation and mutual exclusion analysis.Results:A total of 411 samples of ovarian cancer somatic mutation data were included,among which missense mutation was the most common.SNP accounted for the largest proportion among variant types.In SNV,T>G was the most,T>A was the second.The gene with the highest mutation frequency was TP53,followed by TTN and FLG2.SNP conversions were similar to reverse conversions,and C>T accounted for the highest percentage of the six conversions(35.19%).Enriched pathway analysis:The proportion of samples with mutation in RTK-RAS signaling pathway was 190/411,and the proportion of samples with mutation in Hippo signaling pathway was 147/411.The analysis of the interaction between the TOP50 genes suggested that most of the genes were co-occurring.Conclusions:With TCGA database,this study completed ovarian cancer somatic mutation,which provides some reference for the study of the pathogenesis of ovarian cancer.These studies will promote the understanding of cancer etiology,and also provide a basis for the further study of ctDNA.