Clinical utility of Circulating Long Non-Coding RNAs in indeterminate thyroid nodules

Indeterminate cytology results (Bethesda categories III and IV) from fine-needle aspiration (FNA) create challenges in clinical decision-making. This study evaluated the expression and diagnostic utility of selected long non-coding RNAs (lncRNAs) in cell-free plasma from patients with indeterminate thyroid nodules.

Prospective, single-center study.

Nine candidate long non-coding RNA were selected from a curated disease database. A total of 126 individuals with solitary thyroid nodules were enrolled. RNA was extracted from plasma, FNA, and tissue samples and expression levels were measured using quantitative real-time PCR. In the discovery cohort, patients with benign and malignant nodules confirmed by histopathology, were used to determine optimal cut-off values through receiver operating characteristic analysis. Spearman correlation analyses were performed to assess concordance between plasma and FNA/tissue expression. In the validation phase, significantly altered markers were applied to indeterminate nodules to assess diagnostic performance.

In the discovery cohort, PVT1, MALAT1, and BANCR were significantly upregulated in malignant compared with benign nodules (P < 0.0001). Significant positive correlations were observed between plasma and FNA expression for PVT1 (r = 0.7095), MALAT1 (r = 0.5487), and BANCR (r = 0.6792), and between plasma and tissue expression for PVT1 (r = 0.7673), MALAT1 (r = 0.5284), and BANCR (r = 0.6864) (P < 0.0001). In the Bethesda III/IV validation cohort, only PVT1 retained diagnostic utility, with 76% sensitivity, 87.5% specificity, 85% positive predictive value, and 80% negative predictive value, whereas MALAT1 and BANCR did not demonstrate significant diagnostic performance.

Circulating PVT1 expression in plasma may serve as a useful non-invasive biomarker for distinguishing benign from malignant indeterminate thyroid nodules.