Systematic Reviews
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Sep 26, 2025; 13(27): 104916
Published online Sep 26, 2025. doi: 10.12998/wjcc.v13.i27.104916
Diagnostic accuracy of circulating miR-146, miR-221 and miR-222 in papillary thyroid cancer: A systematic review and meta-analysis
Benjamin Dean, Georgios Geropoulos, Toby Richardson-Jones, Massimiliano Fornasiero, Michail Papapanou, Christos Konstantinidis, Nikolaos Madouros, Dimitrios Spinos, Georgios Koimtzis, Dimitrios Giannis, Christos Athanasiou, Kyriakos Psarras
Benjamin Dean, Georgios Geropoulos, Department of Transplant Surgery, Cambridge University Hospitals, Cambridge CB20QQ, Cambridgeshire, United Kingdom
Benjamin Dean, Toby Richardson-Jones, Medical School, University of Bristol, Bristol BS81QU, United Kingdom
Massimiliano Fornasiero, Medical School, University College London Hospitals, London HA90UL, London, United Kingdom
Michail Papapanou, Second Department of Obstetrics and Gynecology, Medical School, National Kapodistrian University of Athens, Athens 45600, Attikí, Greece
Christos Konstantinidis, Surgical Group, Society of Junior Doctors, Athens 45300, Attikí, Greece
Nikolaos Madouros, Department of Neurosurgery, University College London Hospitalsrs, London HA90OL, United Kingdom
Dimitrios Spinos, Department of Ear, Nose and Throat Surgery, University Hospitals of Birmingham, Birmingham B170NN, United Kingdom
Georgios Koimtzis, Cardiff Transplant Unit, University Hospital of Wales, Cardiff and Vale University Health Board, Cardiff CF144XW, United Kingdom
Dimitrios Giannis, Institute of Health Innovations and Outcomes Research, Feinstein Institutes for Medical Research, Manhasset, NY 11030, United States
Christos Athanasiou, Cambridge University Hospitals, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB34NT, Cambridgeshire, United Kingdom
Kyriakos Psarras, Laboratory of Scientific Research and Experimental Surgery, 2nd Propedeutic Department of Surgery, School of Medicine, Aristotle University, Thessaloniki 54642, Greece
Co-first authors: Benjamin Dean and Georgios Geropoulos.
Author contributions: Dean B, Geropoulos G and Giannis D conceptualized the idea and prepared the first draft; Richardson-Jones T, Fornasiero M, Papapanou M, Konstantinidis C and Madouros N perform the literature search; Geropoulos G, Giannis D, Spinos D and Psarras K critically reviewed the draft and prose the changes; Geropoulos G, Giannis D, Koimtzis G and Athanasiou C prepared the final manuscript and submitted; All authors thoroughly reviewed and endorsed the final manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2020 Checklist, and the manuscript was prepared and revised according to the PRISMA 2020 Checklist.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Dimitrios Giannis, MD, MSc, Institute of Health Innovations and Outcomes Research, Feinstein Institutes for Medical Research, 350 Community Dr, Manhasset, NY 11030, United States. dgiannis@northwell.edu
Received: January 17, 2025
Revised: March 25, 2025
Accepted: July 2, 2025
Published online: September 26, 2025
Processing time: 200 Days and 9.9 Hours
Abstract
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.

Keywords: Micro-RNA; Thyroid cancer; Diagnostics; Systematic review; Meta-analysis

Core Tip: While miRNA levels are strongly associated with papillary thyroid cancer (PTC), no consensus has been reached on their diagnostic accuracy for the condition. This is the first systematic review and meta-analysis assessing statistical strength of miRNA in the diagnosis and staging of PTC. We found that miRNA-146 and miRNA-222 were most sensitive, validating their efficacy in PTC diagnosis.