常见消化系统肿瘤患者TP53和KRAS基因突变的全外显子杂交捕获基因测序及其临床意义  

Sequencing of whole exon hybridization capture genes of TP53 and KRAS mutations in patients with common digestive system tumors and its clinical significance

作　　者：王潇 熊婵玉 张赟 纪娟娟 周玉 WANG Xiao;XIONG Chanyu;ZHANG Yun;JI Juanjuan;ZHOU Yu(Department of Laboratory,Affiliated Hospital,Southwest Medical University,Luzhou 646000,China;Department of Laboratory Medicine and Sichuan Provincial Key Laboratory for Human Disease Gene Study,Sichuan Provincial People’s Hospital,University of Electronic Science and Technology of China,Chengdu 610000,China)

机构地区：[1]西南医科大学附属医院检验科,四川泸州646000 [2]四川省医学科学院·四川省人民医院电子科技大学附属医院临床医学检验中心及人类疾病基因研究四川省重点实验室,四川成都610000

出　　处：《吉林大学学报(医学版)》2025年第2期471-478,共8页Journal of Jilin University:Medicine Edition

基　　金：国家自然科学基金项目(81970825)。

摘　　要：目的:探讨结直肠癌(COAD)、胆管癌(CHOL)、胆囊癌(GBC)、肝细胞癌(LIHC)、胃腺癌(STAD)和胰腺癌(PAAD) 6种常见消化系统肿瘤患者TP53及KRAS基因突变情况,分析TP53和KRAS基因突变与患者不同临床病理特征、肿瘤突变负荷(TMB)及微卫星不稳定(MSI)的关系。方法:收集2022年1月—2023年12月112例经影像学和病理学诊断为6类常见消化系统肿瘤患者的病理石蜡或活检标本,采用基于杂交捕获的基因测序技术检测不同类型肿瘤患者TP53和KRAS基因突变情况,绘制常见消化系统肿瘤样本突变图谱。按照TMB的高低分为高TMB组和低TMB组。比较不同类型消化系统肿瘤患者TP53和KRAS基因突变情况,检测不同临床病理特征患者TP53和KRAS基因突变情况。结果:在112例消化系统肿瘤样本中共检测到276个突变,其中突变率最高的是TP53基因(67%),其次是KRAS基因(34%)。TP53基因在COAD中突变最为显著,其次是LIHC;KRAS基因在PAAD中突变最明显。TP53基因突变主要发生在5~8号外显子上,KRAS基因突变主要发生在2号外显子上。6类消化系统肿瘤中TP53基因突变率比较差异无统计学意义(P>0.05),KRAS基因突变率比较差异有统计学意义(P<0.05)。6类消化系统肿瘤中TP53和KRAS基因共同突变的突变率比较差异有统计学意义(P<0.05)。高TMB和低TMB患者TP53及KRAS基因突变率比较差异有统计学意义(P<0.05);不同性别、年龄、肿瘤大小、分化程度、TNM分期、有无淋巴结和(或)远处转移及MSI患者的TP53及KRAS基因突变率比较差异无统计学意义(P>0.05)。结论:常见消化系统肿瘤中TP53和KRAS基因突变率较高,TP53和KRAS基因突变率与患者肿瘤类型和TMB有一定关联。Objective:To investigate the mutations of TP53 and KRAS genes in the patients with six common types of digestive system tumors,including colorectal cancer(COAD),cholangiocarcinoma(CHOL),gallbladder cancer(GBC),liver hepatocellular carcinoma(LIHC),stomach adenocarcinoma(STAD),and pancreatic adenocarcinoma(PAAD),and to analyze the relationships between TP53 and KRAS gene mutations and clinical pathological characteristics,tumor mutation burden(TMB),and microsatellite instability(MSI)of the patients.Methods:The pathological paraffin or biopsy samples of 112 patients from January 2022 to December 2023 diagnosed with six types of tumors based on imaging and pathology were collected.Hybrid capture-based gene sequencing technology was used to detect TP53 and KRAS gene mutations in the patients with different types of tumors;mutation landscapes of common digestive system tumor samples were constructed.The patients were divided into high and low TMB groups according to the TMB levels.The mutation statuses of TP53 and KRAS genes in the patients with different types of digestive system tumors were compared,and the TP53 and KRAS gene mutations in the patients with different clinicopathological characteristics were examined.Results:A total of 276 mutations were detected in the 112 samples,with the highest mutation rate in TP53 gene(67%),followed by KARS gene(34%).TP53 gene mutation was most prominent in COAD,followed by LIHC,while KRAS gene mutation was most significant in PAAD.TP53 gene mutation mainly occurred in exons 5-8,while the KRAS gene mutation primarily occurred in exon 2.There was no statistically significant difference in TP53 gene mutation rate among the six types of digestive system tumors(P>0.05),while the KRAS gene mutation rate showed statistically significant difference(P<0.05).The mutation rates of TP53 and KRAS gene co-mutation also showed statistically significant difference among the six types of tumors(P<0.05).There were statistically significant differences in TP53 and KRAS gene mutation rates between

关 键 词：消化系统肿瘤 基因突变 TP53基因 KRAS基因 肿瘤突变负荷 微卫星不稳定性 

分 类 号：R735[医药卫生—肿瘤]