不同碘水平下甲状腺结节患者血清外泌体中miRNA生物学标志物的筛选

Screening of miRNA biomarkers in serum exosomes of patients with thyroid nodules at different iodine levels

目的比较不同碘水平下甲状腺结节患者与健康人血清外泌体微小核糖核酸(microRNA,miRNA)表达谱的差异,分析其共同点,为筛选不同碘水平下甲状腺结节早期诊断标志物提供参考依据。方法收集10例不同碘水平下甲状腺结节患者及体检健康者的外周血样本,采用砷铈催化分光光度法测定各组血清碘水平;提取外泌体miRNA,利用高通量测序技术测定血清miRNA的表达水平;预测差异靶基因,并进一步进行GO(Gene ontology)分析和KEGG(Kyoto Encyclopedia of Genes and Genomes)分析。结果在不同碘水平的甲状腺结节患者与健康人群中存在6个表达下调的miRNA,分别为miR-324-5p、miR-6511b-3p、miR-9903、miR-550a-3p、miR-5001-3p、miR-3688-3p。差异表达的外泌体miRNA可调控MAPK信号通路、PI3K-AKT信号通路、VEGF信号通路及NF-κB信号通路。结论筛选出6个差异表达miRNA,有望作为不同碘水平下甲状腺结节早期诊断的生物学标志物。

Objective To comapre and analyze the differences and commonalities of expression profiles of serum exosomal microRNA between patients with thyroid nodules and healthy persons at different iodine levels,and then provide evidence for screening early diagnostic markers of thyroid nodules at different iodine levels.Methods The peripheral blood samples from 10 patients with thyroid nodules and healthy volunteers at different iodine levels were collected.Their serum iodine levels were measured by the arsenic cerium catalytic spectrophotometry.Serum exosomal microRNA were extracted and the expression levels of microRNA were determined by the high-throughput sequencing technology.The differential target genes were predicted and further performed Gene ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis.Results Compared with healthy volunteers,there were 6 downregulated miRNAs in the patients with thyroid nodules at different iodine levels,namely miR-324-5p,miR-6511b-3p,miR-9903,miR-550a-3p,miR-5001-3p,and miR-3688-3p.Differentially expressed exosomal microRNA could regulate the MAPK signaling pathway,PI3K-AKT signaling pathway,VEGF signaling pathway,and NF-κB signaling pathway.Conclusion Six differentially expressed microRNAs is identified,which may serve as biological markers for the early diagnosis of thyroid nodules at different iodine levels.