基于高通量靶向测序技术的肿瘤原发部位差异研究  

Study of differences in tumor primary sites based on high-throughput targeted sequencing technology

作　　者：罗祥 鲁四海 戴鹏高[2] 杨栓盈[1] LUO Xiang;LU Sihai;DAI Penggao;YANG Shuanying(Department of Respiratory Medicine,Second Hospital of Xi’an Jiaotong University,Xi’an 710004,China;The College of Life Sciences,Northwest University,Xi’an 710069,China)

机构地区：[1]西安交通大学第二附属医院呼吸科,陕西西安710004 [2]西北大学生命科学学院,陕西西安710069

出　　处：《西北大学学报（自然科学版）》2023年第4期619-626,共8页Journal of Northwest University（Natural Science Edition）

基　　金：陕西省重点研发计划项目(2022ZDXM-SF-04)。

摘　　要：探究肺内不同病灶部位非小细胞肺癌患者肿瘤突变特征及导致临床表现差异的潜在分子机制。对铜川市人民医院收治的62例肺癌患者的新鲜肿瘤组织标本进行高通量测序,并收集TCGA数据库中502份非小细胞肺癌测序数据,从不同肺叶、分布侧等角度分析基因的突变特征与功能学影响。结果显示,99.1%(559/564)的样本中均检出突变,各标本中双突变比例最高(63.01%~82.93%),各组间均检出特有突变,但其与年龄、性别等无相关性。功能分析表明,叶分组中特有突变参与癌症中心碳代谢、药物抵抗等过程,而左、右侧分组中主要与PD-L1表达调控、细胞增殖、错配修复及凋亡等有关。该研究揭示了原发部位不同的肺癌患者组织突变特征及生物学功能差异,对非小细胞肺癌致病机制研究及临床辅助诊断原发灶具有重要意义。To explore the tumor mutation characteristics of patients with non-small cell lung cancer at different lesion locations in the lung and the underlying molecular mechanisms leading to differences in clinical manifestations.High-throughput sequencing was performed on fresh tumor tissue samples from 62 lung cancer patients admitted to our hospital,and the sequencing data of 502 non-small cell lung cancers in the TCGA database were collected,and the characteristics and functional characteristics of gene mutation were analyzed from the perspectives of different lung lobes and distribution sides.Mutations were detected in 99.1%(559/564)of the samples.The proportion of samples with two mutations detected in different groups is the highest(63.01%~82.93%).There were significant differences in the types and frequencies of mutated genes and loci among the groups,but there was no correlation between them and clinical characteristics(age,gender).The functional prediction results show that the non-shared genes between different lung lobe groups are mainly related to the regulation of carbon metabolism,drug resistance in the cancer center,while the non-shared genes between the left and right lung cancer groups are mainly related to the regulation of PD-L1 expression,cell proliferation,mismatch repair and apoptosis signaling pathway,etc.There are significant differences in tissue mutation characteristics and biological function changes in lung cancer patients with different primary sites,which is of great significance for the study of the pathogenesis of non-small cell lung cancer and the auxiliary clinical diagnosis of the primary tumor.

关 键 词：原发部位 突变 基因功能 高通量测序 非小细胞肺癌 

分 类 号：Q786[生物学—分子生物学]