Biomarker Value of miR-221 and miR-222 as Potential Substrates in the Differential Diagnosis of Papillary Thyroid Cancer Based on Data Synthesis and Bioinformatics Approach

Abstract

BackgroundMicroRNA (miRNA) has been reported to play a critical regulatory role in papillary thyroid carcinomas (PTC). However, the role of miR-221/222 in PTC remains unclear. Here, we performed this study to explore the diagnostic potentials and mechanisms of miR-221/222 in PTC.MethodsFirst, we systematically analyzed the diagnostic value of miR-221/222 in the diagnosis PTC by pooling the published studies. Afterwards, we performed comprehensive bioinformatics analysis including gene ontology analysis, pathway enrichment analysis and protein-protein interaction analysis to explore the potential mechanisms of miR-221/222 involved in PTC.ResultsThe overall sensitivity and specificity of miR-221/222 for PTC were 0.75 (95% CI: 0.70–0.80) and 0.80 (95% CI: 0.76–0.84) respectively with the AUC of 0.85 (95% CI: 0.81-0.88). The diagnostic performance varied among different subgroups including geographical locations, sample sources and sample sizes. Meanwhile, we found that a combination of miR-221/222 and other miRNAs when used in a diagnostic panel could improve the diagnostic accuracy than individual miR-221/222. Moreover, through the bioinformatics analysis, we confirmed that miR-221/222 targets were highly related to the molecular pathogenesis of PTC. The results revealed that miR-221/222 may exert important functions in PTC through thyroid hormone signaling pathway and some other key pathways by regulating some key genes.ConclusionThese findings indicated that miR-221/222 have the potential to serve as auxiliary tools for diagnosing PTC. Further prospective clinical trials should be performed to assess the accuracy of these findings in a larger cohort and determine the clinical uses.

Thyroid Cancer Persistence in Patients with Unreliable Thyroglobulin Measurement: Circulating microRNA as Candidate Alternative Biomarkers

“…Overall, among the different serum miRNAs tested in our study, miRNA 221, 222, and 146b emerged as the most suitable candidate biomarkers to complement imaging (i.e., nUS, Dx-WBS) in the post-operative monitoring of PTC patients with uninformative Tg. This is well in line with some previous reports demonstrating the up-regulation of miR-222, miR-221, and miR-146b in PTC patients compared to those with benign nodules and controls [23][24][25][31][32][33][34][35][36]45]. Rosignolo et al reported that the serum levels of circulating miR-221 were consistent with ATA responses to therapy in PTC patients, supporting their role in post-treatment monitoring [25].…”

“…They included miR-221, miR-222, miR-375, miR-155, and miR-146b, whose circulating levels and tissue expression have been reported to be significantly increased in PTC, with respect to the normal subjects/thyroid tissues in several studies [ 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. In particular, miR-221 and miR-222 are the two most extensively evaluated functional miRNAs in thyroid carcinoma [ 31 ]. Increasing evidence indicates that miR-221, miR-222, and miR-146b are upregulated in PTC [ 24 , 27 ] and their expression significantly predicts the outcome and prognosis of the cancer [ 24 , 27 , 31 , 32 , 33 , 34 , 35 , 36 ].…”

“…In particular, miR-221 and miR-222 are the two most extensively evaluated functional miRNAs in thyroid carcinoma [ 31 ]. Increasing evidence indicates that miR-221, miR-222, and miR-146b are upregulated in PTC [ 24 , 27 ] and their expression significantly predicts the outcome and prognosis of the cancer [ 24 , 27 , 31 , 32 , 33 , 34 , 35 , 36 ].…”

Expression Profile and Diagnostic Significance of MicroRNAs in Papillary Thyroid Cancer

“…Duan et al showed that miR-7-5p and miR-451 can be considered diagnostic biomarkers of PTC [ 89 ]. Additionally, the individual miRNAs that comprise our proposed panel have been previously mentioned as potential biomarkers of PTC [ 14 , 89 , 90 , 91 ]. The overexpression of these miRNAs reflects recent results obtained by Qiao et al, who demonstrated that the combination of five miRNAs, including miR-1296-5p, miR-1301-3p, miR-532-5p, miR-551b-3p, and miR-455-3p, is potentially useful in the diagnosis of PTC (AUC of 0.941 with 82.14% sensitivity and 100% specificity in their study) [ 14 ].…”

Immune-and Metabolism-Associated Molecular Classification of Ovarian Cancer

“…The mechanism OV in C1 subtype patients chiefly involved inositol phosphate metabolism pathway, indicating poor prognosis when contrasted with C2 and C3. Indeed, genes participating in the inositol phosphate metabolism pathway have been incriminated in cancer risk and known to be regulators of cell cycle, metastasis and PI3K/Akt signaling ( 49 ).…”