通过小 RNA 测序鉴定用于诊断甲状腺乳头状癌的外泌体 miRNA 生物标志物。

Identification of exosomal miRNA biomarkers for diagnosis of papillary thyroid cancer by small RNA sequencing.

机构信息

Health Science Center, The First Affiliated Hospital of Shenzhen University, Department of Nuclear Medicine, Institute of Translational Medicine, and Guangdong Key Laboratory of Systems Biology and Synthetic Biology for Urogenital Tumors, Shenzhen Second People's Hospital, Shenzhen, Guangdong, China.

Department of Breast and Thyroid Surgery, Shenzhen Second People's Hospital, Shenzhen, Guangdong, China.

出版信息

Eur J Endocrinol. 2020 Jan;182(1):111-121. doi: 10.1530/EJE-19-0524.

DOI:10.1530/EJE-19-0524

PMID:31721725

Abstract

CONTEXT

Exosomal miRNAs are considered potential non-invasive biomarkers for thyroid cancer. However, the global exosomal miRNAs profile for papillary thyroid cancer (PTC) has not been revealed.

OBJECTIVE

This study investigated the diagnostic value of plasma and serum exosomal miRNAs for PTC.

METHODS

Plasma and serum samples were collected from ten patients with benign thyroid nodules and 17 with PTC for small RNA sequencing. Plasma samples were collected from two independent cohorts, including 119 patients with PTC, 51 healthy people and 82 patients with benign thyroid nodules, for validation by quantitative reverse-transcription polymerase chain reaction (RT-qPCR).

RESULTS

Small RNA sequencing identified 41 putative exosomal miRNA biomarkers for PTC. Twelve miRNAs were selected for validation. miR-376a-3p, miR-4306, miR-4433a-5p, and miR-485-3p expression significantly increased in patients with PTC compared to that in healthy people and patients with benign thyroid nodules (P ˂ 0.05). Moreover, miR-485-3p and miR-4433a-5p presented larger areas under the curve (AUCs). The high expression of exosomal miR-485-3p correlated with tumor size greater than or equal to 1 cm, advanced clinical stage, extrathyroidal extension, BRAF mutation, and lymph node metastasis. Besides, miR-485-3p exhibited the highest AUCs in diagnosing PTC patients with high-risk factors.

CONCLUSIONS

Plasma exosomal miR-485-3p and miR-4433a-5p might serve as biomarkers for PTC diagnosis. Plasma exosomal miR-485-3p could enable discrimination between high-risk and low-risk PTC.

摘要

背景

外泌体 miRNAs 被认为是甲状腺癌潜在的非侵入性生物标志物。然而，尚未揭示甲状腺癌的外泌体 miRNA 全貌。

目的

本研究旨在探讨血浆和血清外泌体 miRNA 对甲状腺癌的诊断价值。

方法

收集了 10 例甲状腺良性结节患者和 17 例甲状腺癌患者的血浆和血清样本进行小 RNA 测序。另外，还收集了两个独立的患者队列的血浆样本，包括 119 例甲状腺癌患者、51 例健康人、82 例甲状腺良性结节患者，通过实时荧光定量聚合酶链反应（RT-qPCR）进行验证。

结果

小 RNA 测序鉴定出 41 个甲状腺癌潜在的外泌体 miRNA 标志物。选择了 12 个 miRNA 进行验证。与健康人及甲状腺良性结节患者相比，甲状腺癌患者的 miR-376a-3p、miR-4306、miR-4433a-5p 和 miR-485-3p 表达明显增加（P ˂ 0.05）。此外，miR-485-3p 和 miR-4433a-5p 的曲线下面积（AUC）较大。外泌体 miR-485-3p 的高表达与肿瘤直径大于或等于 1 cm、临床分期较晚、甲状腺外侵犯、BRAF 突变和淋巴结转移相关。此外，miR-485-3p 在诊断具有高危因素的甲状腺癌患者时 AUCs 最高。