结直肠癌的关键癌症驱动基因筛选及其生物学功能分析

Screening and biological function analysis of key cancer driver genes in colorectal cancer

目的探寻结直肠癌(colorectal carcinoma,CRC)的关键癌症驱动基因(Cancer Driver Genes,CDGs),并探讨其生物学功能。方法从癌症基因组图谱数据库中获取CRC基因组数据,从国际肿瘤基因组协作组数据库获取CRC基因表达数据。利用CRC突变基因数据构建CRC基因突变矩阵,利用突变基因表达数据构建CRC突变基因表达矩阵;从STRING数据库中获取CRC基因的蛋白质相互作用(PPI)网络,运用python软件将CRC基因突变矩阵、CRC突变基因表达矩阵和PPI数据整合,构建CRC高维突变基因加权网络,测算基因最大突变影响分数得分,得到CRC驱动基因,利用CGC数据库筛选CRC关键癌症驱动基因。利用STRING在线分析工具对CRC关键癌症驱动基因进行基因本体分析和京都基因和基因组数据库信号通路富集分析。结果筛选出22个CRC关键癌症驱动基因,分别为ATM、TTN、PCDHGB3、LRP1B、PCDHA6、PIK3CA、SYNE1、PCDHGB2、KMT2C、BRAF、BMPR1A、PCDHGA8、PCDHGA5、FAT4、PCDHA8、APC、PCDHGA7、PCDHA10、PCDHA9及FBXW7。CRC关键癌症驱动基因的分子功能主要集中在钙离子结合、阳离子结合、金属离子结合等;生物过程主要集中在通过质膜黏附分子的同源性细胞黏附、通过质膜黏附分子的细胞—细胞黏附、细胞黏附等;细胞组成主要集中在质膜、质膜的组成部分、膜等;CRC关键癌症驱动基因的信号通路主要集中在大肠癌、FoxO信号通路、调节干细胞多能性的信号通路等。结论CRC关键癌症驱动基因主要有ATM、TTN、PCDHGB3等。CRC关键癌症驱动基因的生物学功能主要集中在钙离子结合、质膜黏附分子的同源性细胞黏附、质膜等;主要通过大肠癌、FoxO信号通路、调节干细胞多能性等信号通路等发挥作用。

Objective To explore the key cancer driver genes(CDGs)of colorectal carcinoma(CRC)and to investigate their biological functions.Methods CRC genomic data were obtained from the Cancer Genome Atlas database,and CRC gene expression data were obtained from the International Tumor Genome Collaboration database.The CRC gene mutation matrix was constructed by using the CRC mutant gene data,and the CRC mutant gene expression matrix was constructed by using the mutant gene expression data.The protein-protein interaction(PPI)network of CRC gene was obtained from the STRING database,and the CRC gene mutation matrix,CRC mutant gene expression matrix and PPI data were integrated by python software to construct a weighted network of CRC high-dimensional mutant genes.The maximum mutation impact score of the gene was measured,the CRC driver gene was obtained,and the key CDGs of CRC were screened by CGC database.The STRING online analysis tool was used to perform gene ontology analysis and Kyoto gene and genome database signal path enrichment analysis on key CDGs of CRC.Results Twenty-two key CDGs of CRC were screened out,namely ATM,TTN,PCDHGB3,LRP1B,PCDHA6,PIK3CA,SYNE1,PCDHGB2,KMT2C,BRAF,BMPR1A,PCDHGA8,PCDHGA5,FAT4,PCDHA8,APC,PCDHGA7,PCDHA10,PCDHA9,and FBXW7.The molecular functions of key CDGs of CRC mainly focused on calcium ion binding,cation binding,metal ion binding,etc.Biological processes mainly focused on homologous cell adhesion through plasma membrane adhesion molecules,cell-cell adhesion through plasma membrane adhesion molecules,and cell adhesion,etc.Cell composition was mainly concentrated in the plasma membrane,the components of the plasma membrane,membranes,etc.The signaling pathways of key CDGs of CRC were mainly concentrated in colorectal cancer,FoxO signaling pathway,and signaling pathways that regulated stem cell pluripotency.Conclusions The key CDGs of CRC mainly include ATM,TTN,PCDHGB3,etc.Their biological functions mainly focus on calcium ion binding,homologous cell adhesion of plasma membrane adhesion molecules,and plasma membrane.They mainly play a role through colorectal cancer,FoxO signaling pathway,regulation of stem cell pluripotency,and other signaling pathways.