基因突变特征与儿童及青少年分化型甲状腺癌远处转移相关性的meta分析

doi:10.19401/j.cnki.1007-3639.2022.05.003

中国癌症杂志 ›› 2022, Vol. 32 ›› Issue (5): 388-396.doi: 10.19401/j.cnki.1007-3639.2022.05.003

基因突变特征与儿童及青少年分化型甲状腺癌远处转移相关性的meta分析

邓姝婷()(), 冯源, 钱凯, 郭凯, 王卓颖()()

上海交通大学医学院附属仁济医院头颈外科,上海 200001

收稿日期:2022-03-25 修回日期:2022-05-01 出版日期:2022-05-30 发布日期:2022-06-09
通信作者: 王卓颖 E-mail:517710910039@shsmu.edu.cn;zhuoyingwang@hotmail.com
作者简介:邓姝婷（ORCID: 0000-0002-2894-5570）,本科 E-mail: 517710910039@shsmu.edu.cn
王卓颖,主任医师,博士研究生导师,现任上海交通大学医学院附属仁济医院头颈外科主任。主要从事甲状腺、唾液腺、软组织及其他头颈部良恶性肿瘤的诊断和治疗的临床及研究工作。担任中国临床肿瘤学会甲状腺癌专家委员会副主任委员,中国抗癌协会头颈肿瘤专业委员会常委。曾获得中国抗癌协会科技奖二等奖、上海市抗癌协会科技奖三等奖、2020年黄浦区领军人才等。主持国家自然科学基金面上项目两项,承担上海市自然科学基金及上海市科技委员会引导项目等,引导上海交通大学医学院“青年科技创新工作室”,负责及参与多项国际及全国多中心临床研究,发表论文50余篇,其中多篇发表在SCI收录期刊上。主编或参与编写论著6部。主持建立了多中心的儿童及青少年甲状腺癌临床数据库,对Hippo通路介导Treg细胞分化发育在调控青少年甲状腺癌淋巴结转移中的作用机制开展了深入研究。目前,已在甲状腺领域权威期刊Thyroid上发表首篇国内儿童及青少年分化型甲状腺癌临床数据及测序分析报道。此外,团队还领导并顺利开展“选择理想的甲状腺乳头状微小癌患者密切随访研究”“BRAF、TERT和RET/PTC基因检测辅助甲状腺结节良恶性诊断的前瞻性及双盲非干预性临床试验”“甲磺酸阿帕替尼片新辅助治疗局部晚期分化型甲状腺癌患者的有效性和安全性研究”等数项国内多中心前瞻性临床研究,建立了甲状腺结节穿刺诊断的多基因联合检测体系,协助甲状腺癌的精准诊断,也为晚期甲状腺癌患者提供了新的药物治疗方案,延长了生存时间,提高了生活质量。
基金资助:
国家自然科学基金(81972496);国家自然科学基金(81772852);上海市自然科学基金(16ZR1406600);2020年度黄浦区领军人才计划;共青团上海交通大学医学院委员会“甲状腺肿瘤防治”青年科技创新工作室

Meta-analysis of the association between gene alterations and distant metastasis of differentiated thyroid carcinoma in children and adolescents

DENG Shuting()(), FENG Yuan, QIAN Kai, GUO Kai, WANG Zhuoying()()

Department of Head and Neck Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200001, China

Received:2022-03-25 Revised:2022-05-01 Published:2022-05-30 Online:2022-06-09
Contact: WANG Zhuoying E-mail:517710910039@shsmu.edu.cn;zhuoyingwang@hotmail.com

摘要/Abstract

摘要：

背景与目的： 甲状腺癌是世界范围内增长率较高的恶性肿瘤之一,在儿童及青少年中甲状腺癌的发病率也在逐年增加。本研究旨在对基因突变特征与儿童及青少年分化型甲状腺癌（differentiated thyroid carcinoma,DTC）远处转移的相关性进行meta分析。方法： 数据库搜索探究基因突变特征与儿童及青少年DTC远处转移相关性的研究,运用STATA 14.0软件分析与远处转移相关的基因突变特征。结果： 纳入20项研究,共涉及1 273例患者,分析结果显示,BRAF V600E突变阴性、RET基因融合阳性是儿童及青少年DTC远处转移的危险因素,而NTRK基因融合与远处转移未见明显相关性。结论： 本研究发现了与儿童及青少年DTC远处转移相关的几个基因突变特征,有利于患者预后的评估及治疗方案的制定。

关键词: 分化型甲状腺癌, 儿童及青少年, 远处转移, 基因突变

Abstract:

Background and purpose: Thyroid cancer is one of the fastest increasing malignancies worldwide, and its incidence in children and adolescents has also been increasing over the years. Meta-analysis were performed to investigate the correlation between gene alteration patterns and distant metastasis of differentiated thyroid carcinoma (DTC) in children and adolescents. Methods: Databases were used to search studies on the association between gene alteration patterns and distant metastasis of DTC in children and adolescents, and STATA 14.0 software was used to analyze the gene alterations related to distant metastasis. Results: Twenty studies involving 1 273 patients were included, and the analysis showed that negative BRAF V600E mutation and positive RET gene fusion were risk factors for distant metastasis in DTC in children and adolescents, while NTRK gene fusion was not significantly associated with distant metastasis. Conclusion: Our research identified several genetic alterations associated with distant metastasis in DTC in children and adolescents, which could be guidance for prognosis assessment and treatment planning.

Key words: Differentiated thyroid cancer, Children and adolescents, Distant metastasis, Gene mutation

中图分类号:

R736.1

邓姝婷, 冯源, 钱凯, 郭凯, 王卓颖. 基因突变特征与儿童及青少年分化型甲状腺癌远处转移相关性的meta分析[J]. 中国癌症杂志, 2022, 32(5): 388-396.

DENG Shuting, FENG Yuan, QIAN Kai, GUO Kai, WANG Zhuoying. Meta-analysis of the association between gene alterations and distant metastasis of differentiated thyroid carcinoma in children and adolescents[J]. China Oncology, 2022, 32(5): 388-396.

图/表 6

图1

表1

纳入文献基本信息"

Author	Published year	Country	Study period	Definition /year	Mean age (range)	Distant metastasis/total (%)	Surgical treatment (%)	RAI/%	Mean follow-up period t/year	Genetic events	Detection method	NOS quality
Sui^[16]	2019	China	2005-2018	≤20	14.54±4.43	40/69 (57.8)	TT (100.0)	100	2.7	BRAF	NR	M
Zhao^[17]	2020	China	2007-2019	≤20	NR	10/77 (13.0)	NR	NR	NR	BRAF	DS	M
Geng^[18]	2019	China	2000-2015	≤14	7.05±1.65	6/39 (15.4)	NR	NR	NR	BRAF	DS	M
Cordioli^[15]	2016	Brazil	1993-2012	≤18	11.36±4.52	10/30 (33.3)	TT (100.0)	NR	NR	AGK-BRAF	RT-PCR	M
Sisdelli^[13]	2019	Brazil	1993-2017	≤18	12.64±4.08	24/80 (30.0)	TT (100.0)	NR	NR	AGK-BRAF	RT-PCR, FISH	M
										BRAF	DS
Chakraborty^[6]	2020	India	2005-2018	≤20	17.00 (14.0-19.0)	17/95 (17.9)	TT (83.2)	33.7	2.5	BRAF	DS	M
							HT (16.8)
Givens^[19]	2014	America	1999-2012	≤18	13.55±3.33	5/19 (26.3)	TT (100.0)	NR	NR	BRAF	Pyrosequencing	H
Geng^[20]	2018	China	1994-2014	≤18	(3.6-13.8)	7/48 (14.6)	TT (56.3)	NR	NR	BRAF	DS	M
							HT (43.7)
Onder^[21]	2016	Turkey	1995-2015	≤18	14.74±3.36	5/50 (10.0)	TT (100.0)	76.0	5.8	BRAF	MASA-PCR	H
Geng^[57]	2019	China	NR	≤18	NR	7/48 (14.6)	TT (56.3)	NR	NR	TERT	DS	L
							HT (43.7)
Stosic^[22]	2021	Canada	NR	≤18	12.80±2.90	11/52 (21.2)	NR	NR	NR	BRAF	MASA-PCR	H
										RET	q-PCR
Franco^[23]	2022	America	1989-2019	≤18	14.53±2.99	22/131 (16.8)	TT (100.0)	65.6	NR	RET	NGS	M
										NTRK
										BRAF
										RAS
Cordioli^[12]	2017	Brazil	NR	≤18	11.80±4.48	13/35 (37.1)	TT (100.0)	NR	NR	BRAF	DS	H
										NTRK	RT-PCR
										AGK-BRAF	RT-PCR, FISH
										RET	RT-PCR
Alzahrani^[24]	2020	Saudi	2004-2019	≤18	17.00 (5.0-18.0)	5/48(10.4)	TT (100.0)	89.6	10.8	BRAF	NGS	M
										RET
Potter^[25]	2021	America	2005-2016	≤24	NR	10/36 (27.8)	NR	94.0	NR	BRAF	NGS	M
										RET
										NTRK
Lee^[26]	2021	Korea	1983-2020	≤20	14.30±3.80	20/106 (18.9)	NR	NR	7.3	RET	Various methods	M
										NTRK
										ALK
										BRAF
Pekova^[27]	2020	Czech	2003-2019	≤20	14.50±3.40	10/93 (10.8)	TT (88.2)	90.3	6.0	RET	NGS,RT-PCR	M
							ST (11.8)			NTRK
										ALK
										BRAF
Alzahrani^[28]	2017	Saudi	1998-2015	≤18	15.50 (8.0-18.0)	9/79 (11.4)	TT (100.0)	92.4	5.4	BRAF	DS	M
Pekova^[29]	2019	Czech	2003-2017	≤20	14.2±3.4	10/83 (12.0)	TT (86.7)	86.7	6.0	RET	RT-PCR	H
							HT (13.3)			BRAF	NGS
Alzahrani^[30]	2016	Saudi	NR	≤18	16.00 (9.0-18.0)	8/55 (14.5)	TT (100.0)	89	NR	BRAF	DS	M

表1

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基因突变特征与儿童及青少年分化型甲状腺癌远处转移相关性的meta分析

Meta-analysis of the association between gene alterations and distant metastasis of differentiated thyroid carcinoma in children and adolescents

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