甲状腺乳头状癌潜在关键基因的生物信息学分析

Bioinformatics analysis of potential hub genes in papillary thyroid carcinoma

背景与目的甲状腺癌是近年来发病率增长最快的疾病,甲状腺乳头状癌(PTC)是甲状腺癌最多见的一种亚型。目前,亟需寻找与PTC相关的生物标志物分子,以提高预后诊断和提供高效的治疗靶标。方法检索并分析GEO数据库PTC相关的的微阵列数据集(GSE60542,GSE33630和GSE3467),通过GEO数据库的GEO2R工具筛选PTC和正常甲状腺组织的差异表达基因。对差异基因行全基因组的富集分析,这些差异基因蛋白质之间的相互作用通过线上数据库工具分析,通过Cytoscape软件进行可视化处理。通过Cbioportal分析工具评估关键基因对PTC的预后价值并进一步行实验验证。结果共鉴定62个上调和40个下调差异基因,挑选出10个具有高度连通性的关键基因,其中,KIT降低与PTC的预后不良相关(P<0.01)。通过qRT-PCR检测52例PTC组织和癌旁正常组织中KIT的表达,结果显示,KIT在癌组织中表达较癌旁正常组织显著降低(P<0.001),KIT的表达与临床分期(P=0.008)和淋巴结转移明显相关(P=0.023)。结论KIT在PTC组织中表达较正常甲状腺组织降低,其可能是PTC患者预后不良的关键基因,并有望成为PTC的治疗靶标和分子生物学标志物。

Background and Aims Thyroid cancer is the disease with the fastest increase in incidence in recent years.Papillary thyroid carcinoma(PTC)is the most common subtype of thyroid cancer.There is an urgent need to find relevant biomarker molecules of PTC,so as to improve the prognosis diagnosis and provide highly specific therapeutic targets.Methods The microarray data sets(GSE60542,GSE33630 and GSE3467)related to PTC in GEO database were retrieved and analyzed,and the differentially expressed genes between PTC and normal thyroid tissue were screed using the GEO2R tool of the GEO database.The genome-wide enrichment analysis of differential genes was performed,and the interactions of proteins of these differential genes were analyzed by online database tools and visualized by Cytoscape software.The prognostic values of the hub genes for PTC were evaluated by Cbioportal analysis tool and further verified by validation experiments.Results A total of 62 up-regulated and 40 down-regulated differential genes were identified,and 10 hub genes with high connectivity were selected.Among the hub genes,the decrease of KIT was associated with poor prognosis of PTC(P<0.01).The expression of KIT was detected in 52 specimens of PTC tissue and normal adjacent tissue by qRT-PCR.The results showed that the expression of KIT in PTC tissue was significantly lower than that in normal adjacent tissue(P<0.001);the expression of KIT was significantly related to the clinical stage(P=0.008)and lymph node metastasis(P=0.023).Conclusion The expression of KIT in PTC is lower than that in normal tissues.It is probably a key gene for poor prognosis of PTC patients,and is expected to serve as a therapeutic target and molecular biomarker.