A Panel of Plasma Exosomal miRNAs as Potential Biomarkers for Differential Diagnosis of Thyroid Nodules

Abstract

Background: A liquid biopsy using circulating exosomal genetic materials provides new insights for thyroid cancer diagnosis. This study aimed to identify plasma-derived exosomal biomarkers that could be used for early detection of papillary thyroid carcinoma (PTC). Method: Exosomal miRNAs in plasma were isolated from patients with benign thyroid nodules and patients with PTC. Profiling of exosomal miRNA was performed using RNA sequencing (RNA-seq) to identify miRNA candidates and differentiate the benign from malignant. The validation cohort consisted of 30 patients with benign thyroid nodules, 35 PTC patients, and 31 healthy individuals. Real-time PCR was used to quantify the expression of miRNA candidates. The diagnostic potential of the candidates was evaluated by receiver operating characteristic (ROC) curves. Results: After RNA-seq, eight plasma exosomal miRNAs were selected as candidates. Further validation indicated that the levels of exosomal miR-16-2-3p, miR-223-5p, miR-34c-5p, miR-182-5p, miR-223-3p, and miR-146b-5p were significantly lower in nodules compared to healthy controls (p < 0.0001), whereas miR-16-2-3p and miR-223-5p were significantly higher in the PTC cases than in those with benign nodules (p < 0.05). ROC analyses revealed that the above six miRNAs were potent indicators for detection of thyroid nodules. Meanwhile, miR-16-2-3p and miR-223-5p can be utilized for detecting PTC from benign nodules. Additionally, combined miRNA panels showed increased diagnostic sensitivities and specificities compared to single miRNA markers. Conclusion: Six aberrantly expressed plasma exosomal miRNAs may be used as diagnostic biomarkers to differentiate thyroid nodules from healthy individuals. The panel consisting of miR-16-2-3p, miR-223-5p, miR-101-3p, and miR-34c-5p are eligible for discriminating benign from malignant thyroid nodules.

Long non-coding RNA DUXAP8 promotes the cell proliferation, migration, and invasion of papillary thyroid carcinoma via miR-223-3p mediated regulation of CXCR4

“…For example, miR-223-3p repressed the metastasis and progression of osteosarcoma cells by targeting CDH6 [ 20 ], over-expression of miR-223-3p suppressed the proliferation, invasion, and migration of breast cancer cells by targeting the ECT2 oncogene [ 21 ]. More interestingly, a previous study demonstrated that lower expression of miR-223-3p was found in benign thyroid nodules and PTC in comparison with healthy subjects [ 30 ]. Consistent with previous researches, our study demonstrated that the up-regulation of miR-223-3p blocked the malignant phenotype of PTC cells.…”

Exosomes as New Biomarkers and Drug Delivery Tools for the Prevention and Treatment of Various Diseases: Current Perspectives

“…Plasma exocrine miR-485-3p can distinguish between high-risk and low-risk PTCs [99]. By analyzing exocrine bodies from different patients and screening a group of miRNAs in plasma exocrine bodies, Li MH et al found that the combination of these miRNAs was more effective than any single marker in identifying PTC and thyroid nodules [100]. These results suggest that the comprehensive detection of various exocrine contents may be more advantageous.…”

The Role of Exosomes in Thyroid Cancer and Their Potential Clinical Application

“…Plasma exosomal miR-485-3p could enable discrimination between high-risk and low-risk PTCs (62). Li MH et al screened a panel of miRNAs in plasma exosomes by analyzing exosomes from different patients and found that the combination of these miRNAs is more effective in identifying PTC and thyroid nodules than any single marker (63). These results suggest that the comprehensive detection of multiple exosome contents may be more advantageous.…”