Evaluation of plasma exosomal miRNAs as potential diagnostic biomarkers of lymph node metastasis in papillary thyroid carcinoma

Endocrine. 2021 Dec 1. doi: 10.1007/s12020-021-02949-x. Online ahead of print.

Abstract

Purpose: The early diagnosis of lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC) is clinically important, as it can aid in treatment decision-making and improve prognosis. In the present study, we aimed to identify whether plasma exosomal miRNAs could be potential diagnostic markers of LNM in PTC.

Methods: Profiles of plasma exosomal miRNAs were screened using miRNA microarrays. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed in the validation and diagnostic sets to select candidate exosomal miRNAs. Finally, receiver operating characteristic (ROC) curves were generated to evaluate the efficiency of target exosomal miRNAs in distinguishing PTC-N1 patients from PTC-N0 patients.

Results: In total, 197 miRNAs were found to be differentially expressed in the testing set. Based on the qRT-PCR results, the expression of miR-6774-3p (p < 0.001) and miR-6879-5p (p < 0.001) in the PTC-N1 patients was significantly higher than that in the controls. The AUC values of plasma exosomal miR-6774-3p (0.802; 95% CI, 0.724-0.879) and miR-6879-5p (0.787; 95% CI, 0.706-0.867) and their combination (0.914; 95% CI, 0.865-0.962) were higher than those of the total miRNAs directly isolated from plasma. Moreover, the expression of exosomal miRNAs was stable after treatment with RNase A, prolonged incubation, or repeated freezing and thawing.

Conclusions: The two plasma exosomal miRNAs (miR-6774-3p and miR-6879-5p) and their combination could serve as new promising biomarkers for the diagnosis of LNM in PTC patients.

Keywords: biomarkers; exosomal miRNAs; lymph node metastasis; papillary thyroid carcinoma; total miRNAs.