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中华普通外科学文献(电子版) ›› 2020, Vol. 14 ›› Issue (05) : 394 -400. doi: 10.3877/cma.j.issn.1674-0793.2020.05.020

所属专题： 专题评论； 文献；

循证医学

促甲状腺激素受体突变与分化型甲状腺癌相关性的系统评价
笪东祝1, 龙智2, 王倩2, 乔高昂1, 刘俊1,†()   
  1. 1. 211166　上海，南京医科大学附属上海市第一人民医院临床医学院；201620　上海市第一人民医院乳腺甲状腺血管外科
    2. 201620　上海市第一人民医院儿内科
  • 收稿日期:2020-03-23 出版日期:2020-10-01
  • 通信作者: 刘俊
  • 基金资助:
    上海市松江区科学技术委员会资助项目(19SJKJGG17)

Correlation between thyroid stimulating hormone receptor mutations and differentiated thyroid cancer: A systematic review

Dongzhu Da1, Zhi Long2, Qian Wang2, Gaoang Qiao1, Jun Liu1,†()   

  1. 1. Nanjing Medical University of Shanghai General Hospital, Nanjing 211166, China; Department of Breast-Thyroid-Vascular Surgery, Shanghai General Hospital, Shanghai 201620, China
    2. Department of Pediatrics, Shanghai General Hospital, Shanghai 201620, China
  • Received:2020-03-23 Published:2020-10-01
  • Corresponding author: Jun Liu
  • About author:
    Corresponding author: Liu Jun, Email:
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引用本文：

笪东祝, 龙智, 王倩, 乔高昂, 刘俊. 促甲状腺激素受体突变与分化型甲状腺癌相关性的系统评价[J]. 中华普通外科学文献(电子版), 2020, 14(05): 394-400.

Dongzhu Da, Zhi Long, Qian Wang, Gaoang Qiao, Jun Liu. Correlation between thyroid stimulating hormone receptor mutations and differentiated thyroid cancer: A systematic review[J]. Chinese Archives of General Surgery(Electronic Edition), 2020, 14(05): 394-400.

目的

系统评价分化型甲状腺癌（DTC）患者中促甲状腺激素受体（TSHR）基因突变的情况。

方法

检索PubMed、Web of Science、Cochrane Library、中国知网、万方数据库有关对DTC患者进行TSHR基因突变检测的研究，检索时限自建库至2020年4月4日，对纳入文献提取相关数据进行分析，并获得DTC患者TSHR基因突变谱。

结果

共纳入27个研究，包括395个DTC组织样本。TSHR突变频率为10.38%（41/395），其中92.68%（38/41）的突变发生在第10外显子上，M453T发生突变频率最高（6/37，16.22%），其次是F458S（4/37，10.81%）。在描述甲状腺功能状况的50例DTC中，81.82%（18/22）的合并甲状腺功能亢进（甲亢）/亚甲亢患者发生TSHR突变，明显高于甲状腺功能正常者的10.71%（3/28），差异有统计学意义（χ2=25.569，P<0.001）。

结论

DTC中TSHR突变并不罕见，特别是在低TSH水平下更易出现。TSHR突变可能与DTC发生有关，特别是在合并甲亢情况下。

关键词: 受体，促甲状腺素释放激素, 突变, 甲状腺肿瘤, 系统评价
Objective

To systematically evaluate the mutations of thyroid stimulating hormone receptor (TSHR) genes in patients with differentiated thyroid cancer (DTC).

Methods

A computerized literature search was carried out in PubMed, Web of Science, Cochrane Library, CNKI and Wanfang Data to identify all relevant cases of TSHR gene mutations in DTC patients. The search time period was from the establishment of the database to April 4, 2020. The relevant data extracted from the literature were analyzed, and the TSHR gene mutation profile of DTC patients was obtained.

Results

A total of 27 studies were included, including 395 DTC tissue samples. TSHR mutations were found in 10.38% (41/395) of DTC tissue samples, of which 92.68% mutations occurred in exon 10. M453T had the highest mutation frequency (6/37, 16.22%), followed by F458S (4/37, 10.81%). In addition, in 50 cases of DTC describing thyroid function, TSH mutations occurred in 81.82% (18/22) tissue samples with hyperthyroidism/subclinical hyperthyroidism, which was significantly higher than 10.71% (3/28) of normal thyroid function.

Conclusions

TSHR mutations in DTC are not uncommon, especially at low TSH levels. TSHR mutations may be related to the occurrence of DTC, especially DTC with hyperthyroidism.

Key words: Receptors, thyrotropin-releasing hormone, Mutation, Thyroid neoplasms, Systematic review
图1 文献检索及结果流程图
表1 与DTC相关的TSHR突变
作者及年份 外显子测序 肿瘤样本数 平均年龄(岁) 性别(M/F) 肿瘤类型 甲状腺功能 突变频次 突变外显子 突变位点 等位基因频率(%) 氨基酸变化 备注
Cross等2008[5] Exon10 1 29 0/1 PTC 甲亢 1 Exon10 c.1867G>T N/A p.Ala623Ser (A623S) 肺、脑、LN转移
Blackburn等2018[6] N/A 1 12 0/1 FTC 甲亢 1 Exon10 c.1703T>C 25 p.Ile568Thr (I568T) 未转移
Russo等1997[7] Exon1-10 1 60 0/1 岛状癌 甲亢 1 Exon10 c.1896G>C N/A p.Asp633His (D633H) LN和双肺转移
Kocsis-Deak等2020[8] N/A 39 50.6 8/31 PTC N/A 4 Exon10 c.1373T>C 5.91 5.94 7.34 11.16 p.Phe458Ser (F458S) ?
? ? ? ? ? ? ? 2 Exon10 c.1397A>T 5.59 10.94 p.Tyr466Phe (Y466F) ?
? ? ? ? ? ? ? 1 Exon10 c.1864_ 1865insAA 8.42 p.Ile622fs ?
Xu等2019[9] Exon1-10 15 N/A 2/13 PTC N/A 1 Exon10 c.1358T>C N/A p.Met453Thr (M453T) ?
Duan等2019[10] N/A 53 46 16/37 FTC N/A 0 — — — — 术前2例远处转移
Nicolson等2018[11] Exon1-10 39 55.2 13/26 FTC N/A 1 Exon10 c.1458C>G 33.3 p.Ile486Met (I486M) 随访中肺转移，BRAF-WT
? ? ? ? ? ? ? 1 Exon9 c.842G>A 23.5 p.Ser281Asn (S281N) 未转移BRAF-WT
? ? ? ? ? ? ? 1 Exon10 c.1888A>C 36.7 p.Ile630Leu (I630L) BRAF-WT
? ? ? ? ? ? ? 1 Exon10 c.1358T>C 39.1 p.Met453Thr (M453T) 未转移BRAF-WT
Mon等2018[12] N/A 4 53 0/1 PTC 正常 1 Exon10 c.1915C>T 37 p.Pro639Ser (P639S) BRAF（+）
? ? ? 64 1/0 FTC 甲亢 1 Exon10 c.1702A>T 42.8 p.Ile568Phe (I568F) ?
? ? ? 59 1/0 ? 亚甲亢 1 Exon10 c.1888A>C 45 p.Ile630Leu (I630L) ?
? ? ? 48 1/0 ? 甲亢 1 Exon10 N/A 36.3 p.Phe631Leu (F631L) ?
Jung等2016[13] Exon1-10 13 51 4/9 FTC N/A 0 — — — — ?
Pagan等2016[14] N/A 62 N/A N/A 12FTC 50PTC N/A 1 Exon10 c.1358T>C N/A p.Met453Thr (M453T) 突变为FTC
Tong等2015[15] N/A 1 89 0/1 FTC 正常 1 Exon9 c.814C>G N/A p.Leu272Val (L272V) 腰大肌转移灶；BRAF-WT
Campenni等2015[16] Exon1-10 1 36 1/0 PTC 甲亢 0 — — — — 未转移
Eszlinger等2014[17] Exon9-10 4 16 1/3 PTC 正常 1 Exon10 c.1895C>T N/A p.Thr632Ile (T632I) ?
Nikiforova等2013[18] Exon10 57 N/A N/A PTC N/A 1 Exon10 N/A N/A N/A ?
? ? 36 N/A N/A FTC N/A 4 Exon10 其中之一：c.1893C>A N/A 其中之一p.Phe631Leu (F631L) ?
Ruggeri等2013[19] N/A 1 15 0/1 PTC 甲亢 1 Exon7 c.561T>C 9 p.Ile187Ile (I187I) 同义突变
Lado-Abeal等2010[20] Exon8-10 1 55 0/1 FTC 甲亢 1 Exon10 c.1358T>C N/A p.Met453Thr (M453T) 未转移BRAF-WT
Nishihara等2009[21] Exon9-10 4 48.3 0/4 PTC 甲亢 1 Exon10 c.1358T>C N/A p.Met453Thr (M453T) ?
? ? ? ? ? ? 甲亢 1 Exon10 c.1458C>G N/A p.Ile486Met (I486M) ?
? ? ? ? ? ? 亚甲亢 1 Exon10 c.1899C>A N/A p.Asp633Glu (D633E) ?
Niepomniszcze等2006[22] Exon10 1 64 0/1 FTC 甲亢 1 Exon10 c.1859C>T N/A p.Thr620Ile (T620I) Ki-RAS G12C突变
Gozu等2004[23] 部分Exon10 1 N/A 0/1 PTC 甲亢 1 Exon10 c.1535T>G N/A p.Leu512Arg (L512R) ?
Fuhrer等2003[24] Exon9-10 1 59 1/0 FTC 亚甲亢 1 Exon10 c.1897G>T N/A p.Asp633Tyr (D633Y) H-和K-ras-WT肺转移灶TSHR-WT
? ? 1 ? ? ? ? 1 Exon10 c.18991T>A N/A p.Phe631Ile (F631I) ?
Camacho等2000[25] Exon9-10 1 49 0/1 FTC 甲亢 1 Exon10 c.1456A>T N/A p.Ile486Phe (I486F) ?
Mircescu等2000[26] Exon10 1 11 0/1 PTC 甲亢 1 Exon10 c.1358T>C N/A p.Met453Thr (M453T) ?
Tonacchera等1999[27] Exon9-10 2 N/A N/A 1FTC 1PTC 正常 0 — — — — ?
Russo等1999[28] Exon10 1 42 0/1 FTC 亚甲亢 1 Exon10 c.2029C>G N/A p.Leu677Val (L677V) Ras-WT
Cetani等1999[29] Exon9-10 22 41.7 11/11 8FTC 14PTC 正常 0 — — — — ?
Esapa等1997[30] 部分Exon10 2 N/A N/A FTC N/A 0 — — — — ?
Spambalg等1996[31] Exon10 29 N/A N/A 21FTC 8PTC N/A 1 Exon10 c.1894A>G N/A p.Thr632Ala (T632A) 5例有转移，其中1例有突变突变均FTC
? ? ? ? ? ? ? 1 Exon10 c.1895C>T N/A p.Thr632Ile (T632I) ?
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