摘要
目的研究抑癌基因TP53突变型和野生型结直肠腺癌的临床病理和基因突变谱差异。方法从cBioPortal数据库下载TCGA结直肠腺癌数据资料(GDAC Firehose),根据抑癌基因TP53突变状态将其分为突变型和野生型2种亚型。统计分析2种亚型的临床病理特征差异和基因突变谱差异,并分析差异基因及差异基因蛋白的相互作用。结果220例结直肠腺癌中有120例肿瘤存在TP53基因突变,突变率为54.5%。临床病理特征分析结果显示,TP53基因突变多发于左半结肠和直肠,基因组变异片段>5%的例数显著增多,而高突变负荷的肿瘤比例显著减少(P<0.05)。LRP1B、FAT4、FBXW7、PIK3CA等25个基因在TP53野生型结直肠癌中的突变率明显增高,String分析表明基因EP300、KMT2A、CREBBP、NOTCH之间存在紧密连接,基因BRAF、PIK3CA、PDGFRA、VAV1之间存在紧密连接。基因本体(GO)功能注释和京都基因和基因组百科全书(KEGG)通路富集分析发现,差异基因主要与DNA结合、转录调控等分子功能相关,并主要富集在PDGFR、EGFR、VEGFR、PI3K等信号通路。结论除发生部位外,TP53突变型和野生型结直肠腺癌存在相似的临床病理形态学特征。但TP53突变型结直肠癌更容易发生染色体不稳定性;而TP53野生型结直肠癌突变负荷增高,可通过产生新的基因突变,激活非p53信号通路促进肿瘤生长。
Objective To explore the differences of clinicopathology and gene mutation spectrum in TP53 mutant and wildtype colorectal adenocarcinoma.Methods TCGA colorectal cancer data(GDAC Firehose)were downloaded from cBioPortal database.According to the mutation status of TP53 gene,colorectal cancers were divided into 2 subtypes:the mutant type and the wild type.The differences in clinicopathology and gene mutation profiles of the 2 subtypes were statistically analyzed.We analyzed differential genes and the interaction between differential gene proteins.Results Of the 220 colorectal cancers,120 had TP53 gene mutation,with a mutation rate of 54.5%.Analysis of clinicopathologic characteristics showed that TP53 gene mutation mostly occurred in left colon and rectum,and the number of cases with genome variant fragments>5% increased significantly,while the number of tumors with high mutation burden decreased significantly(P<0.05).The mutation rates of 25 genes including LRP1B,FAT4,FBXW7 and PIK3CA increased significantly in TP53 wild-type colorectal cancer.String analysis showed that there were close connections among EP300,KMT2A,CREBBP and NOTCH,as well as among BRAF,PIK3CA,PDGFRA and VAV1.GO function annotation and KEGG pathway enrichment analysis showed that differential genes were mainly related to such molecular functions as DNA binding and transcription regulation,and were mainly enriched in signal pathways such as PDGFR,EGFR,VEGFR,and PI3K.Conclusion The TP53 mutant and wild-type colorectal cancer had similar clinicopathological characteristics except for the location.However,TP53 mutant colorectal cancer was more likely to have chromosomal instability;while TP53 wild-type colorectal cancer had an increased mutational burden,which could generate new gene mutations and activate non-p53 signaling pathways to promote tumor growth.
作者
孙耀华
王瀚
李雪莹
杨慧玲
白辰光
Sun Yaohua;Wang Han;Li Xueying;Yang Huiling;Bai Chenguang(Department of Pathology,Changhai Hospital,Naval Military Medical University,Shanghai 200433,China)
出处
《海军医学杂志》
2021年第3期304-309,共6页
Journal of Navy Medicine
基金
上海卫生计生系统重要薄弱学科建设计划(2015ZB0202)。
