肺腺癌和肺鳞癌中mRNA可变剪接特征的比较  

Comparison of alternative splicing in lung adenocarcinoma and lung squamous carcinoma

作　　者：陈梦竹[1] 王秀杰[2] 夏立新[1] Chen Mengzhu Wang Xiujie and Xia Lixin(State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Health Science Center, Shenzhen University, Shenzhen 518060, Guangdong Province, P. R. China Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, P. R. China)

机构地区：[1]深圳大学医学部,呼吸疾病国家重点实验室深圳大学变态反应分室,广东深圳518060 [2]中国科学院遗传与发育生物学研究所,北京100101

出　　处：《深圳大学学报（理工版）》2017年第1期33-45,共13页Journal of Shenzhen University(Science and Engineering)

基　　金：国家高技术研究发展计划资助项目(2012AA020409);深圳市知识创新计划基础研究资助项目(JCYJ20150525092941055)~~

摘　　要：利用SUPPA(a super-fast pipeline for alternative splicing)软件分析癌症基因组数据库癌基因组图谱中肺腺癌和肺鳞癌样本的RNA-Seq数据,发现在鉴定的7种主要可变剪接转录本中外显子跳跃转录本发生频率最高.通过癌组织与癌旁组织的比较,系统地鉴定了肺腺癌和肺鳞癌中差异表达的可变剪接转录本,发现约60%的差异可变剪接转录本是两种肺癌亚型所共有的.功能富集分析表明,癌组织特异的可变剪接转录本主要富集在细胞周期调控、脱氧核糖核酸代谢和核糖核酸代谢等生物过程中,而癌旁组织特异的可变剪接转录本则主要富集在囊泡介导转运、多肽转运和脂质转运等生物过程中.通过肺癌驱动基因可变剪接转录本的比较分析,鉴定了两种肺癌亚型共有或特有的可能具有癌驱动功能的可变剪接转录本.Lung cancer is a common disease with high morbidity and mortality. Studies have shown that alternative splicing （AS） is closely associated with lung carcinogenesis, but the difference of alternative splicing between lung adenocarcinoma （LUAD） and lung squamous carcinoma （LUSC） remains unclear. Here, we analyze the RNA-Seq data of LUAD and LUSC from TCGA using SUPPA software, and find that skipping exon （SE） is the most frequently occurred AS transcript among seven main AS transcripts identified. By comparing tumor tissues with normal ones, we systematically identify differentially expressed AS transcripts in both LUAD and LUSC, of which around 60% are identical between these two subtypes. Functional analysis reveals that tumor-specific AS transcripts are mainly enriched among genes associated with cell cycle regulation, deoxyribonucleic acid metabolism and RNA metabolism, whereas normal-specific AS transcripts are enriched among genes mainly involved in vesicle-mediated transport,peptide transport and lipid transport. By comparing AS transcripts of cancer-driven genes between LUAD and LUSC, we identify some common and subtype-specific AS transcripts with cancer-driven potentiality.

关 键 词：生物信息学 肺腺癌 肺鳞癌 可变剪接 外显子跳跃 可变起始外显子 

分 类 号：R734.2[医药卫生—肿瘤] Q811.4[医药卫生—临床医学]