甲状腺乳头癌中的 BRAF 突变、BRAF 激活的长链非编码 RNA 和 miR-9 的表达及其与临床病理特征的关系。
BRAF mutation, BRAF-activated long non-coding RNA and miR-9 expression in papillary thyroid carcinoma, and their association with clinicopathological features.
机构信息
The Fourth Department of General Surgery, the Second Affiliated Hospital, Harbin Medical University, 246 Xuefu Road, Harbin, 150001, Heilongjiang Province, China.
The Department of Head and Neck Surgery, General Hospital of Heilongjiang Province Land Reclamation Bureau, Harbin, 150088, Heilongjiang Province, China.
出版信息
World J Surg Oncol. 2020 Jun 27;18(1):145. doi: 10.1186/s12957-020-01923-7.
BACKGROUND
The incidence of thyroid cancer is increasing worldwide. This study investigated the association of B-type RAF kinase (BRAF) mutation status, the expression of BRAF-activated long non-coding RNA (BANCR) and microRNA miR-9, and the clinicopathological features of papillary thyroid carcinoma (PTC).
METHODS
Clinicopathological data for PTC patients (n = 51) diagnosed and treated between 2018 and 2019 were collected. Carcinoma and adjacent normal tissue samples were analyzed for the presence of the BRAF mutation and/or expression of BANCR and miR-9.
RESULTS
Larger tumor, higher rate of bilateral tumors and multifocality, extracapsular invasion, and lateral lymph node metastasis (LNM) were observed in PTC patients with BRAF mutation. Patients with higher BANCR expression had a higher rate of extracapsular invasion and lateral LNM in carcinoma tissue and a lower frequency of bilateral tumors and multifocality in normal adjacent tissue. Patients with higher miR-9 expression had a lower rate of central and lateral LNM in carcinoma tissue and higher rates of bilateral tumor location and multifocality in normal adjacent tissue. Patients with BRAF mutation have a higher rate of BANCR overexpression and tended to have a lower rate of miR-9 overexpression (P = 0.057), and a negative association was observed between BANCR and miR-9 expression in carcinoma tissue.
CONCLUSIONS
BRAF mutation and the BANCR and miR-9 expression were closely associated with the tumor size, bilateral tumor location, multifocality, extracapsular invasion, and lateral LNM. PTC patients with these clinicopathological characteristics, BRAFV600E mutation, and high BANCR expression and low miR-9 expression needed earlier surgical treatment and are recommended for total thyroidectomy in primary surgery for reducing the risk of recurrence. These findings provide new insight into the molecular basis for PTC and can inform strategies for the management of PTC.
背景
全球范围内甲状腺癌的发病率正在增加。本研究调查了 B 型 RAF 激酶（BRAF）突变状态、BRAF 激活的长非编码 RNA（BANCR）和 microRNA miR-9 的表达与甲状腺乳头状癌（PTC）的临床病理特征之间的关系。
方法
收集了 2018 年至 2019 年间诊断和治疗的 PTC 患者（n=51）的临床病理数据。分析了癌组织和相邻正常组织样本中 BRAF 突变的存在情况以及 BANCR 和 miR-9 的表达情况。
结果
BRAF 突变的 PTC 患者的肿瘤更大、双侧肿瘤和多灶性、包膜外侵犯和侧方淋巴结转移（LNM）的发生率更高。癌组织中 BANCR 表达较高的患者包膜外侵犯和侧方 LNM 的发生率更高，而正常相邻组织中双侧肿瘤和多灶性的发生率更低。miR-9 表达较高的患者癌组织中中央和侧方 LNM 的发生率较低，正常相邻组织中双侧肿瘤位置和多灶性的发生率较高。BRAF 突变患者 BANCR 过表达的发生率较高，且 miR-9 过表达的发生率较低（P=0.057），癌组织中 BANCR 和 miR-9 的表达呈负相关。
结论
BRAF 突变以及 BANCR 和 miR-9 的表达与肿瘤大小、双侧肿瘤位置、多灶性、包膜外侵犯和侧方 LNM 密切相关。具有这些临床病理特征、BRAFV600E 突变和高 BANCR 表达及低 miR-9 表达的 PTC 患者需要更早的手术治疗，并建议在初次手术中进行全甲状腺切除术，以降低复发风险。这些发现为 PTC 的分子基础提供了新的认识，并可为 PTC 的管理策略提供参考。
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