Li Xize, Qin Wen, Wang Wenting, Liu Weilin, Dong Tianyi, Liu Aixiang, Cai Haojie, Xu Zhouhan, Zeng Jiping
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Jinan, 250012, People's Republic of China.
The Hospital Wing, Shandong University, Jinan, 250012, People's Republic of China.
Onco Targets Ther. 2024 Dec 10;17:1173-1185. doi: 10.2147/OTT.S489559. eCollection 2024.
MiRNAs play a pivotal role in tumorigenesis and development by exerting negative regulation on the expression of target genes. In this study, bioinformatics techniques and online database were employed to investigate the specific miRNA-target gene regulatory network in PTC, which was subsequently validated using human blood samples and compared to existing tumor markers.
The miRNA (GSE50901) and Gene Expression (GSE113629) chip screening data of human PTC tissues were retrieved from GEO database. A comparative analysis was conducted using the GEO2R to identify differentially expressed miRNAs and target genes of the patients with PTC. Prediction of the miRNA-target gene regulatory network, related signal transduction pathways, biological effects and their relationship to prognosis was performed based on GO, KEGG, qRT-PCR detection of human blood samples, analysis of correlation on the existing pathological tumor markers, and ROC.
Compared to the corresponding normal thyroid tissues, a total of 2116 miRNAs were found to be differentially expressed in PTC patients, including 1968 up-regulated and 148 down-regulated genes. The abnormally expressed genes primarily participated in signal pathways associated with tumorigenesis and abnormal gene transcription. By utilizing data from the GEO database, five miRNAs closely linked to PTC prognosis were identified, which were miR-221-3p, miR-222-3p, miR-182-5p, miR-135a-5p, and miR-34a-5p, with elucidating the target genes. Experimental validation, correlation analysis with tumor markers along with bioinformatics analysis revealed a significant increase in expression levels of miR-182-5p in PTC patients which positively correlated with poor prognosis. These molecules could play crucial roles in both initiation and progression of PTC.
This study identified potential novel blood-based miRNA biomarkers for PTC through bioinformatics analysis combined with the detection of human blood samples, thereby offering new possibilities for significant biomarkers associated with diagnosis and prognosis of PTC.
微小RNA(miRNA)通过对靶基因表达进行负调控,在肿瘤发生和发展过程中发挥关键作用。本研究运用生物信息学技术和在线数据库,探究甲状腺乳头状癌(PTC)中特定的miRNA-靶基因调控网络,随后使用人体血液样本进行验证,并与现有的肿瘤标志物进行比较。
从基因表达综合数据库(GEO数据库)中检索人类PTC组织的miRNA(GSE50901)和基因表达(GSE113629)芯片筛选数据。使用GEO2R进行比较分析,以鉴定PTC患者中差异表达的miRNA和靶基因。基于基因本体论(GO)、京都基因与基因组百科全书(KEGG)、对人体血液样本进行定量逆转录聚合酶链反应(qRT-PCR)检测、分析与现有病理肿瘤标志物的相关性以及受试者工作特征曲线(ROC),对miRNA-靶基因调控网络、相关信号转导通路、生物学效应及其与预后的关系进行预测。
与相应的正常甲状腺组织相比,共发现2116个miRNA在PTC患者中差异表达,其中1968个基因上调,148个基因下调。异常表达的基因主要参与与肿瘤发生和异常基因转录相关的信号通路。利用GEO数据库的数据,鉴定出与PTC预后密切相关的5个miRNA,即miR-221-3p、miR-222-3p、miR-182-5p、miR-135a-5p和miR-34a-5p,并阐明了其靶基因。实验验证、与肿瘤标志物的相关性分析以及生物信息学分析显示,PTC患者中miR-182-5p的表达水平显著升高,且与不良预后呈正相关。这些分子可能在PTC的起始和进展中发挥关键作用。
本研究通过生物信息学分析结合人体血液样本检测,鉴定出潜在的新型基于血液的PTC miRNA生物标志物,从而为与PTC诊断和预后相关的重要生物标志物提供了新的可能性。