Expression Profile and Diagnostic Significance of MicroRNAs in Papillary Thyroid Cancer

Abstract

The incidence of papillary thyroid cancer (PTC) has increased in recent years. To improve the diagnostic management of PTC, we propose the use of microRNAs (miRNAs) as a biomarker. Our aim in this study was to evaluate the miRNA expression pattern in PTC using NanoString technology. We identified ten miRNAs deregulated in PTC compared with reference tissue: miR-146b-5p, miR-221-3p, miR-221-5p, miR-34-5p, miR-551b-3p, miR-152-3p, miR-15a-5p, miR-31-5p, and miR-7-5p (FDR < 0.05; |fold change (FC)| ≥ 1.5). The gene ontology (GO) analysis of differentially expressed miRNA (DEM) target genes identified the predominant involvement of epidermal growth factor receptor (EGFR), tyrosine kinase inhibitor resistance, and pathways in cancer in PTC. The highest area under the receiver operating characteristic (ROC) curve (AUC) for DEMs was found for miR-146-5p (AUC = 0.770) expression, indicating possible clinical applicability in PTC diagnosis. The combination of four miRNAs (miR-152-3p, miR-221-3p, miR-551b-3p, and miR-7-5p) showed an AUC of 0.841. Validation by real-time quantitative polymerase chain reactions (qRT-PCRs) confirmed our findings. The introduction of an miRNA diagnostic panel based on the results of our study may help to improve therapeutic decision making for questionable cases. The use of miRNAs as biomarkers of PTC may become an aspect of personalized medicine.

Differential microRNA expression for diagnosis and prognosis of papillary thyroid cancer

“…Papillary thyroid cancer can be diagnosed with an ultrasound, FNA, and cytology testing. However, it is sometimes impossible to differentiate between malignant and benign tissue at a preoperative stage ( 4 ). Some investigations have revealed that the expression of specific miRNAs can be associated with characteristics such as tumor size, capsular and vascular invasion, and tumor aggressiveness ( 47 ).…”

“…Rogucki and colleagues have shown that a panel of four miRNAs (miR-152-3p, miR-221-3p, miR-551b-3p, and miR-7-5p) could be used for the diagnosis of PTC. Furthermore, miR-152-3p, miR-221-3p, and miR-7-5p target EGFR gene regulation ( 4 ). The EGFR gene is a tyrosine kinase involved in cell proliferation, and mutations in this gene are associated with PTC tumor cell development ( 48 ).…”

“…One of the conventional diagnostic methods is ultrasound, which detects thyroid nodules in approximately 68% of PTC patients ( 4 ). Another diagnostic method is an ultrasound-guided fine needle aspiration biopsy (FNA), which has limitations and may lead to inconclusive results ( 5 ).…”

“…microRNAs (miRNAs) are small non-coding molecules of approximately 19 to 24 nucleotides related to gene regulation. Alteration of some of these miRNAs has been associated with the expression of pathological features in PTC and gene dysregulation in PTC tumor-promoting cells ( 4 ). Hence, obtaining specific miRNA expression patterns may improve the patient’s diagnosis using less invasive methods ( 6 ).…”

MicroRNA expression profiling of RAS-mutant thyroid tumors with follicular architecture: microRNA signatures to discriminate benign from malignant lesions

“…In fact, it is known that RAS mutations influence miRNA expression profiles in thyroid tumors [22,23]. However, authors mostly focused on differential miRNA expression between malignant and benign tumors, without considering the presence of RAS mutations as a confounding factor [24][25][26]; on the contrary, several miRNAs are known to be specifically deregulated in BRAF mutant thyroid tumors compared to wild-type cases [27,28]. In previous studies from our group, we demonstrated that wild-type NIFTPs show a benign-like miRNA phenotype, while RAS-mutant NIFTPs show a malignant-like miRNA phenotype [29,30]; in detail, 12 miRNAs were significantly deregulated in mutant versus wild-type NIFTPs (miR-221-5p, miR-221-3p, miR-222-3p, miR-146b-5p, miR-181a-3p, miR-28-5p, miR-363-3p, miR-342-3p, miR-1285-5p, miR-152-3p, miR-25-3p, miR-30e-3p) [30].…”