运用生物信息学筛选甲状腺乳头状癌生物靶点

Screening key biomarkers in papillary thyroid carcinoma:evidence from bioinformatic analysis

目的进一步了解甲状腺乳头状癌(papillary thyroid carcinoma,PTC)发生发展的生物分子机制,寻找新的临床病理特征判断依据以及预后评价和靶向治疗的新分子靶点。方法通过分析基因表达综合数据库(GEO)中相关样本的基因芯片数据,筛选出PTC与正常甲状腺组织细胞中的差异表达基因(the differentially expressed genes,DEGs)。运用STRING及DAVID在线数据库对DEGs进行蛋白互作(the protein-protein interaction,PPI)网络分析、GO功能和生物学途径富集通路分析以及KEGG代谢通路分析,并从中筛选出关键基因。结果本研究共筛选出339个DEGs及10个关键基因,其中FN1、CCND1、TIMP1、ICAM1、APOE、MET、RUNX2、KRT19和SERPINA1在PTC中的表达上调,KIT在PTC中的表达下调。在对假设检验做多重检验校正后,可得APOE[错误发现率(false discover rate,FDR)=0.0475]及KIT(FDR=0.0420)基因表达的改变对PTC患者的无复发生存期(recurrence-free-survival,RFS)有一定的影响,具有统计学意义。结论FN1、ICAM1、APOE、MET、KRT19、KIT和SERPINA1基因相对高表达的改变可能与PTC的预后有关。但需要进一步的研究来具体阐明这些基因在PTC发生发展过程中的生物作用机制。

Objective To understand the molecular mechanisms underlying the carcinogenesis and progression of papillary thyroid carcinoma(PTC),and provide candidate targets for diagnosis and treatment of PTC.Methods To identify the differentially expressed genes(DEGs)in the carcinogenesis and progression of PTC,the study was carried by analyzing the microarray datasets downloaded from gene expression omnibus(GEO)database,and making a series of studies including the protein-protein interaction network,KEGG and GO enrichment analyses of DEGs.Results A total of 339 DEGs and 10 hub genes were identified.While the expression of KIT was downregulated in the samples of PTC,the figures for FN1,CCND1,TIMP1,ICAM1,APOE,MET,RUNX2,KRT19 and SERPINA1 were upregulated.After the hypothesis test was corrected by multiple tests,the results showed that the changes of APOE[false discovery rate(FDR)=0.0475]and KIT(FDR=0.0420)gene expression had a certain impact on recurrence free survival(RFS)of PTC patients,which was statistically significant.Conclusions Survival analysis showed that FN1,ICAM1,APOE,MET,KRT19,KIT and SERPINA1 may be involved in the carcinogenesis or prognosis of PTC.However,further studies are needed to elucidate the biological function of these genes in PTC.