甲状腺微小乳头状癌潜在高风险侵袭性的生物信息学初步分析  

Preliminary analysis on the potentially high-risk invasiveness of PTMC by bioinformatics

作　　者：廉猛[1] 杨帆[2] 张嘉敏 陈佳铭 沈茜茜 侯丽珍[1] 刘晓琴 房居高[1] LLAN Meng;YANG Fan;ZHANG Jiamin;CHEN Jiaming;SHEN Qianqian;HOU Lizhen;LIU Xiaoqin;FANG Jugao(Department of Otolaryngology Head and Neck Surgery,Beijing Tongren Hospital,Capital Medical University,Bejjing 100730,China;Department of Otolaryngology Head and Neck Surgery,Beijing Anzhen Hospital,Capital Medical University,Beijing,100029,China;Department of Otolaryngology,Inner Mongolia People1s Hospital,Hohhot,Inner Mongolia,010010,China)

机构地区：[1]首都医科大学附属北京同仁医院耳鼻咽喉头颈外科,北京100730 [2]首都医科大学附属北京安贞医院耳鼻咽喉头颈外科,北京100029 [3]内蒙古自治区人民医院耳鼻咽喉科,内蒙古呼和浩特010010

出　　处：《中国耳鼻咽喉头颈外科》2020年第8期451-456,共6页Chinese Archives of Otolaryngology-Head and Neck Surgery

基　　金：北京市医管局培育计划(PX2018009);北京市中医局科技发展资金项目(QN2018-32);中华国际医学交流基金会甲状腺中青年医生研究项目(2017-N-14);2017年度内蒙古自治区卫生计生科研计划(201703007);首都卫生发展科研专项自主创新项目(2018-2-2054)。

摘　　要：目的基于转录组测序技术筛选甲状腺微小乳头状癌潜在高风险侵袭性相关的差异表达基因,生物信息学进一步分析探讨具有调控作用的分子通路并寻找功能性靶向基因.方法应用转录组测序技术对15例潜在高风险侵袭性(7例局部淋巴结转移,3例腺体外组织侵犯,5例多癌灶)和9例惰性甲状腺微小乳头状癌进行差异表达基因的筛查,并对差异基因进一步行生物信息学在线分析.结果共筛选出1269个差异基因.经GO数据库分析,差异基因主要聚类在趋化性、细胞黏附、细胞-基质黏附、钙黏蛋白结合等集合中(P<0.05);经KEGG数据库分析,肌动蛋白细胞骨架调节通路(regulation of actin cytoskeleton)、细胞的焦点粘连通路(focal adhesion)、PI3K-Akt信号通路(PI3K-Akt signaling pathway)、黏着小带通路(adherens junction)以及癌症途径通路(pathways in cancer)差异基因富集的显著程度高(P<0.05),是应关注的关键通路;其中,功能性下调基因ITGA2、ITGA3和ITGAV差异表达明显,富集程度较高,处于信号通路的核心调控位置,是与PTMC潜在高风险侵袭性相关的重要基因(P<0.05).结论与惰性PTMC相比,具有潜在高风险侵袭性特征的PTMC在基因表达的整体模式上存在明显差异,而整合素家族的ITGA2、ITGA3和ITGAV基因是需要重点关注的与PTMC潜在高风险侵袭性相关的功能性靶向基因.OBJECTIVE Through differentially expressed genes analysis in papillary thyroid microcarcinoma(PTMC) samples with potentially high-risk invasiveness,we want to explore the underlying regulatory pathways and potentially functional target genes by bioinformatics.METHODS A total of 24 PTMC tissue samples were selected,including15 cases with potentially high-risk invasiveness(7 cases of local lymph node metastasis,3 cases of in vitro glandular tissue invasion,5 cases of multiple cancerous foci) and 9 indolent cases.The differently expressed genes were collected,screened and bioinformatical analyzed.RESULTS A total of 1269 differential genes were screened.According to GO database analysis,the differential genes were clustered mainly in the groups of chemotaxis,cell adhesion,cell-matrix adhesion,and cadherin binding(P<0.05).According to KEGG database analysis,regulation of actin cytoskeleton pathway,the focal adhesion pathway,PI3K-Akt signaling pathway,adhesion band pathway and cancer pathway showed the significantly differential expression between tested group and control group(P<0.05).Among these analysis,the functionally down-regulated genes of ITGA2,ITGA3,and ITGAV were significantly differentially expressed,with the highest degree of enrichment.These genes were believed to be highly related to the invasiveness of PTMC(P<0.05) and to be in the key positions of the signaling pathways.CONCLUSIONCompared with indolent PTMC,PTMC with potentially high-risk invasiveness was significantly differentially expressed in the overall gene expression pattern,and ITGA2,ITGA3,and ITGAV of the integrin family were believed to be highly related with potential high risk of PTMC,which should be researched further.

关 键 词：甲状腺肿瘤 甲状腺微小乳头状癌 转录组测序 生物信息学 

分 类 号：R736.1[医药卫生—肿瘤]