Beyond Biopsy: Could Nrf2 and microRNA-222 Redefine Thyroid Nodule Diagnosis?
Abstract
Thyroid nodules are common and present a diagnostic challenge. Fine-needle aspiration cytology (FNAC) is frequently used but may yield indeterminate results. Molecular biomarkers such as Nuclear factor erythroid 2–related factor 2 (Nrf2) and microRNA 222 (miR 222) have emerged as promising tools to improve diagnostic accuracy. A case-control study was conducted on 87 subjects: 16 patients with papillary thyroid carcinoma (PTC), 39 patients with benign thyroid disorders, and 32 healthy controls. The study was conducted at Safeer Al-Imam Al-Hussain (A.S) Surgical Hospital and Al-Kafeel Superspeciality Hospital in Kerbala city.Serum Nrf2 levels were measured using ELISA, while miR 222 expression was analyzed using RT-PCR. Fold change (FC) of miR 222 showed the highest sensitivity (96.88%) and NPV (83.33%) in detecting simple nodules, with an AUC of 0.650. Ct miR 222 demonstrated the highest specificity (83.33%) and PPV (89.47%), making it useful as a confirmatory marker. Nrf2 exhibited poor diagnostic performance (AUC = 0.480). In multinodular cases, both Nrf2 and FC miR 222 showed fair discrimination ability (AUCs ≈ 0.636–0.637). The study confirms the high prevalence of multifocal benign nodularity in PTC patients (61.8%). Overall, the modest AUC values for all markers suggest that no single biomarker is sufficient for definitive diagnosis of thyroid nodules. The choice of biomarker depends on clinical objectives: FC microRNA-222 for maximizing detection (screening) and Ct.microRNA-222 (for simple nodules) or Nrf2 (for multi-nodules) for confirming diagnoses and minimizing false positives. Future research should focus on combining these biomarkers into panels to improve diagnostic accuracy.
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