Xize Li,1,* Wen Qin,2,* Wenting Wang,1 Weilin Liu,1 Tianyi Dong,3 Aixiang Liu,4 Haojie Cai,1 Zhouhan Xu,1 Jiping Zeng1,5 

1Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Jinan, 250012, People’s Republic of China; 2The Hospital Wing, Shandong University, Jinan, 250012, People’s Republic of China; 3Department of Breast and Thyroid Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, People’s Republic of China; 4Department of Clinical Laboratory, Zaozhuang Municipal Hospital, Zaozhuang, 277102, People’s Republic of China; 5School of Health and Life Sciences, University of Health and Rehabilitation Sciences, Qingdao, 266113, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Jiping Zeng, Email zengjiping@uor.edu.cn

Objective: 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.
Methods: 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.
Results: 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.
Conclusion: 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.

Keywords: papillary thyroid carcinoma, microRNA, differentially expressed genes, bioinformatics, blood samples