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. 2020 Feb 13:13:1311-1319.
doi: 10.2147/OTT.S231361. eCollection 2020.

Plasma Exosomal miR-146b-5p and miR-222-3p are Potential Biomarkers for Lymph Node Metastasis in Papillary Thyroid Carcinomas

Ke Jiang  1 , Genpeng Li  1 , Wenjie Chen  1 , Linlin Song  1 , Tao Wei  1 , Zhihui Li  1 , Rixiang Gong  1 , Jianyong Lei  1 , Hubing Shi  2 , Jingqiang Zhu  1
Affiliations

Plasma Exosomal miR-146b-5p and miR-222-3p are Potential Biomarkers for Lymph Node Metastasis in Papillary Thyroid Carcinomas

Ke Jiang et al. Onco Targets Ther. .

Abstract

Background: Lymph node metastasis (LNM) is associated with increased risk of recurrence and poor prognosis in papillary thyroid cancer (PTC). Novel non-invasive biomarkers for the prediction of LNM in PTC patients are still urgently needed. In this study, the relationship between the expression of plasma exosomal microRNAs (miRNAs) and LNM was analyzed. Further, we aimed to explore if exosomal miRNAs can serve as indicators of LNM in PTC patients.

Methods: A total of 64 PTC patients who underwent total thyroidectomy and neck dissection from June 2018 to July 2018 in West China Hospital were enrolled in this study. Plasma exosomes were isolated by exoRNeasy Serum/Plasma Maxi Kit. The levels of selected exosomal miRNAs were detected by real-time quantitative PCR (qRT-PCR). Cox proportional hazard analyses and receiver operating characteristic (ROC) curves were conducted to evaluate the predictive efficiency. Furthermore, PTC cell lines with transfection of miRNA mimics/inhibitors were used to verify the functions of exosomal miRNAs.

Results: 49 PTC patients with LNM and 15 without LNM were included in the present study. Exosomal miR-146b-5p and miR-222-3p were both significantly upregulated in patients with LNM (P values were 0.008 and 0.015, respectively). ROC analyses revealed that the areas under the curves (AUCs) of miR-146b-5p and miR-222-3p for LNM prediction were 0.811 and 0.834, respectively. Moreover, the AUC increased to 0.895 when the two miRNAs used together. Wound healing assays and transwell assays showed that miR-146b-5p and miR-222-3p significantly enhanced the migration and invasion ability of PTC cells in vitro.

Conclusion: Plasma exosomal miR-146b-5p and miR-222-3p could serve as potential biomarkers for LNM in PTC.

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

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Conflict of interest statement

No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.

Figures

Figure 1
Figure 1
(A–J) Relative expressions of ten exosomal miRNAs in PTC patients with or without LNM by qRT-PCR (exosomal miR-21-5p, miR-146b-5p, miR-204-5p, miR-221-3p, miR-222-3p were significantly higher in LNM group when compared with the group without LNM).
Figure 2
Figure 2
Receiver operating characteristic curves for exosomal miR-146b-5p and miR-222-3p to predict LNM.
Figure 3
Figure 3
(A–D) Overexpression of miR-146b-5p enhanced migration and invasion of PTC cells. **p values < 0.01; ***p values < 0.001.
Figure 4
Figure 4
(A–D) Overexpression of miR-222-3p promoted migration and invasion of PTC cells. ***p values < 0.001.
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