Diagnostic accuracy of circulating miR-146, miR-221 and miR-222 in papillary thyroid cancer: A systematic review and meta-analysis.

Background: Papillary thyroid cancer (PTC) often recurs following surgical excision, necessitating reliable long-term screening techniques after initial management. Ultrasound scans have a poor predictive value and biopsy and genetic testing have a low sensitivity. Biomarker detection, including thyroglobulin, has reduced accuracy as residual thyroid tissue remains following surgery. Serum/tissue microRNA detection offers a promising alternative to screen for thyroid malignancy. Based on our previous systematic review, miR-146, miR-221 and miR-222 appear most strongly associated with PTC.

Aim: To perform a systematic review and meta-analysis, evaluating the use of circulating miR-146, miRNA-221 and miR-222 in PTC diagnosis and staging.

Methods: A systematic literature search of MEDLINE, Scopus and the EMBASE library was performed. Human participants of any age, sex or geographical distribution were considered. Original studies assessing the diagnostic and prognostic accuracy of circulating serum miRNAs in histologically-confirmed PTC were included. Proportion and regression meta-analyses (logit-transformed) were conducted. PRISMA guidelines were followed throughout the process.

Results: Among the 1530 studies screened, 6 met the inclusion criteria, reporting non-overlapping populations. For the diagnosis of PTC vs benign nodules (BN), the pooled sensitivity of miR-146 was 80.7% (95%CI: 65.2%-90.4%), specificity was 66.9% (95%CI: 55.5%-76.6%), and false positive rate was 33.1% (95%CI: 23.4%-44.5%). Pooled sensitivity, specificity and false positive rate of miR-222 for diagnosis of PTC vs BN was 64.3% (95%CI: 50.3%-76.2%), 88.8% (95%CI: 82.4%-93%) and 11.2% (95%CI: 7%-17.6%) respectively. Pooled sensitivity, specificity and false positive rate of miR-221 in this population demonstrated reduced accuracy. Pooled sensitivity and specificity of PTC vs healthy controls for total serum miRNAs were 82% (95%CI: 77%-86%) and 84% (95%CI: 76%-90%) respectively. The summary area under receiver operating characteristic curve value for the same analysis was 0.89 (95%CI: 0.86-0.92).

Conclusion: miRNA-146 and miRNA-222 were most sensitive, validating their efficacy in PTC diagnosis. Larger studies are needed for confident population generalisability. Use of two-MRNA types in conjunction needs to be assessed.