Cohort study on correlation between serum TTF-1, PAX-8 and thyroid dysfunction after breast cancer post-operative radiation therapy

Gang CHEN; Shunkang ZHANG; Shaowen GUO; Yue LU; Liyun SUN; Lei SHEN; Cheng WANG

doi:10.19401/j.cnki.1007-3639.2024.12.004

您当前的位置：

首页 >

文章列表页 >

Cohort study on correlation between serum TTF-1, PAX-8 and thyroid dysfunction after breast cancer post-operative radiation therapy

Article | 更新时间：2025-12-31

- Cohort study on correlation between serum TTF-1, PAX-8 and thyroid dysfunction after breast cancer post-operative radiation therapy
- China Oncology Vol. 34, Issue 12, Pages: 1100-1107(2024)
- 作者机构：
  
  1. 上海交通大学医学院附属第九人民医院黄浦分院放疗科，上海 200011
  2. 上海交通大学医学院附属第九人民医院黄浦分院中心实验室，上海 200011
  3. 上海交通大学医学院附属第九人民医院黄浦分院乳腺外科，上海 200011
- 作者简介：
  
  WANG Cheng
- 基金信息：
- DOI：10.19401/j.cnki.1007-3639.2024.12.004
  CLC：
- Received：26 September 2024，
  
  Published：30 December 2024
- 稿件说明：
移动端阅览
Gang CHEN, Shunkang ZHANG, Shaowen GUO, et al. Cohort study on correlation between serum TTF-1, PAX-8 and thyroid dysfunction after breast cancer post-operative radiation therapy[J]. China Oncology, 2024, 34(12): 1100-1107.
DOI：

Gang CHEN, Shunkang ZHANG, Shaowen GUO, et al. Cohort study on correlation between serum TTF-1, PAX-8 and thyroid dysfunction after breast cancer post-operative radiation therapy[J]. China Oncology, 2024, 34(12): 1100-1107. DOI： 10.19401/j.cnki.1007-3639.2024.12.004.

摘要

背景与目的：

甲状腺功能异常在乳腺癌术后放疗患者的长期随访中较为常见。本研究旨在结合血清学甲状腺功能指标的检查结果，比较乳腺癌术后患者在放疗前后甲状腺转录因子-1（thyroid transcription factor-1，TTF-1）和配对盒转录因子8（paired box 8，PAX-8）血清水平的变化，分析两种甲状腺转录因子血清水平的变化与乳腺癌术后放疗后出现甲状腺功能异常的相关性。

方法：

前瞻性选取上海交通大学医学院附属第九人民医院黄浦分院放疗科2022年1月—2022年6月收治的无甲状腺疾病史且在乳腺癌术后接受放疗的女性患者，按照有无锁骨上区放疗野分成两组。所有患者入组前均被完整告知研究内容，并签署知情同意书。本研究设计通过了上海交通大学医学院附属第九人民医院黄浦分院伦理委员会的伦理审查（审批号：伦审2021-KY-2）。分别记录入组患者放疗前、放疗结束时、放疗结束后6、12和24个月两种甲状腺转录因子（TTF-1、PAX-8）的血清水平、血清甲状腺功能指标的检查结果，包括三碘甲状腺原氨酸（triiodothyronine，T3）、四碘甲状腺原氨酸（tetraiodothyronine，T4）、游离三碘甲状腺原氨酸（free triiodothyronine，FT3）、游离四碘甲状腺原氨酸（free tetraiodothyronine，FT4）、促甲状腺激素（thyroid stimulating hormone，TSH）、甲状腺过氧化物酶抗体（thyroid peroxidase antibody，TPO-Ab）。本研究严格遵循《加强流行病学中观察性研究报告质量》指南中的各项条目。

结果：

共80例患者入组（每组各40例）。两组患者中有19例发生甲状腺功能减退，其中锁骨上区野放疗组15例，无锁骨上区野放疗组4例（

=0.004）。两组患者放疗前血清TTF-1[5.70（5.11，7.13）

6.68（5.15，7.57），

=0.296

]

、PAX-8（5.26±1.01

5.66±1.37，

=0.149）水平差异无统计学意义。其中锁骨上区野放疗组患者TTF-1、PAX-8的血清检测值在放疗结束后的12个月内逐渐升高;而无锁骨上区野放疗组TTF-1、PAX-8的

血清水平在放疗结束后的24个月内无明显变化。两组患者的TTF-1的血清检测值在放疗结束后6个月[6.99（4.73，13.94）

5.79（5.01，6.28），

=0.049

]

、12个月[7.65（5.02，17.85）

5.43（4.52，6.22），

=0.005

]

的差异均有统计学意义;PAX-8的血清检测值在放疗后12个月[6.79（4.86，14.30）

5.81（4.70，7.25），

=0.042

]

的差异有统计学意义。以锁骨上区野放疗组TTF-1以及PAX-8均明显升高的放疗结束后12个月的检测值中位数作为参考数值，将检测值超过平均值的患者定义为甲状腺转录因子升高亚组，低于平均值定义为甲状腺转录因子正常亚组，比较两个亚组中甲状腺功能减退发生情况的差异，并分析锁骨上区野放疗组患者TTF-1/PAX-8升高与甲状腺功能减退发生的相关性，结果显示升高亚组的甲状腺功能减退发生率明显高于正常亚组（分别为65.0%

10.0%、60.0%

15%，

=0.001、

=0.008）。多因素分析结果显示乳腺癌术后锁骨上区野放疗结束后12个月的TTF-1/PAX-8升高与甲状腺功能减退的发生呈正相关（OR=9.702、OR=3.930，

=0.020、

=0.046）。

结论：

乳腺癌术后放疗引起的甲状腺功能异常主要表现为甲状腺功能减退;乳腺癌术后锁骨上区野放疗显著增加患者甲状腺功能减退的发生率;而在乳腺癌术后锁骨上区野放疗后甲状腺功能减退的患者中，甲状腺转录因子TTF-1和PAX-8的血清水平显著增高。

Abstract

Background and purpose:

Thyroid dysfunction can frequently be discovered in breast cancer patients during long-term follow-up after receiving post-operative radiation therapy (PORT). This study aimed to compare serum levels of thyroid transcription factors (TTFs) TTF-1 and paired box 8 (PAX-8) before and after PORT in breast cancer patients

combined with the results of serological thyroid indicators tests

and to analyze the relationship between the changes in serum levels of these two kinds of TTFs and thyroid dysfunction after breast cancer PORT.

Methods:

Female breast cancer patients without thyroid disease records who received PORT in Department of Radiation Oncology

Shanghai Ninth People’s Hospital Huangpu Branch

Shanghai Jiao Tong University School of Medicine from Jan. 2022 to Jun. 2022 were prospectively selected

and were divided into two groups according to being with or without supraclavicular radiation field. All the patients had given informed consent before joining the study. The study design was approved by t

he ethic committee of our hospital (Ethic Approval No. 2021-KY-2). Serum levels of TTF-1 and PAX-8

serological thyroid indicators [triiodothyronine (T3)

tetraiodothyronine (T4)

free triiodothyronine (FT3)

free tetraiodothyronine (FT4)

thyroid stimulating hormone (TSH) and thyroid peroxidase antibody (TPO-Ab)

]

were recorded before PORT

at the end of PORT

12 and 24 months after the end of PORT

respectively. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist was followed for this study.

Results:

Eighty patients were enrolled in this study (40 in each group). A total of 19 patients who had hypothyroidism were divided in two groups

15 in supraclavicular field group (SC group) and 4 in non-supraclavicular field group (NSC group)

respectively (

=0.004). Levels of TTF-1 [5.70 (5.11

7.13)

6.68 (5.15

7.57)

=0.296

]

and PAX-8 (5.26±1.01

5.66±1.37

=0.149) did not show statistically significant deference between two groups before PORT. In SC group

levels of TTF-1 and PAX-8 gradually rose in 12 months after the end of PORT. In NCS group

levels of TTF-1 and PAX-8 did not change significantly during 24 months after the end of PORT. Test results of serum TTF-1 between two groups were statistically different at 6 months [6.99 (4.73

13.94)

5.79 (5.01

6.28)

=0.049

]

12 months [7.65 (5.02

17.85)

5.43 (4.52

6.22)

=0.005

]

after the end of PORT

while test results of serum PAX-8 between two groups were statistically different at 12 months [6.79 (4.86

14.30)

5.81 (4.70

7.25)

=0.042

]

after the end of PORT. The median values of TTF-1 and PAX-8 test results at 12 months after the end of PORT in SC group which were both significantly higher compared with NSC group were selected as the referent thresholds. Patients in SC group whose test results were higher tha

n referent thresholds were defined as TTF-1/PAX-8 elevating subgroups

and patients whose test results under the threshold defined as TTF-1/PAX-8 normal subgroups. The incidences of hypothyroidism were higher in elevation subgroups than in normal subgroups (65.0%

10.0%

60.0%

15.0%

respectively

=0.001

=0.008

respectively). Positive correlations were observed between the elevation of TTF-1/PAX-8 at 12 months after the end of PORT and hypothyroidism after breast cancer supraclavicular field radiation (

=9.702

3.930

and

=0.020

0.046

respectively) according to multivariate analysis.

Conclusion:

Thyroid dysfunction after breast cancer PORT was mainly manifested with hypothyroidism; supraclavicular field radiation may significantly increase the incidence of hypothyroidism; serum levels of TTF-1 and PAX-8 elevated obviously in breast cancer PORT patients who had hypothyroidism after receiving supraclavicular field radiation.

关键词

Keywords

references

WEISS A , CHAVEZ-MACGREGOR M , LICHTENSZTAJN D Y , et al . Validation study of the American Joint Committee on Cancer eighth edition prognostic stage compared with the anatomic stage in breast cancer [J ] . JAMA Oncol , 2018 , 4 ( 2 ): 203 - 209 . DOI: 10.1001/jamaoncol.2017.4298 http://doi.org/10.1001/jamaoncol.2017.4298

SUNG H , FERLAY J , SIEGEL R L , et al . Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J ] . CA Cancer J Clin , 2021 , 71 ( 3 ): 209 - 249 .

中国抗癌协会乳腺癌专业委员会 , 中华医学会肿瘤学分会乳腺肿瘤学组 . 中国抗癌协会乳腺癌诊治指南与规范(2024年版) [J ] . 中国癌症杂志 , 2023 , 33 ( 12 ): 1092 - 1187 . DOI: 10.19401/j.cnki.1007-3639.2023.12.004 http://doi.org/10.19401/j.cnki.1007-3639.2023.12.004

The Society of Breast Cancer China Anti-Cancer Association , Breast Oncology Group of the Oncology Branch of the Chinese Medical Association . Guidelines for breast cancer diagnosis and treatment by China Anti-Cancer Association (2024 edition) [J ] . Chin Oncol , 2023 , 33 ( 12 ): 1092 - 1187 . DOI: 10.19401/j.cnki.1007-3639.2023.12.004 http://doi.org/10.19401/j.cnki.1007-3639.2023.12.004

SAJI M , SHONG M , NAPOLITANO G , et al . Regulation of major histocompatibility complex class Ⅰ gene expression in thyroid cells. Role of the cAMP response element-like sequence [J ] . J Biol Chem , 1997 , 272 ( 32 ): 20096 - 20107 .

NAPOLITANO G , MONTANI V , GIULIANI C , et al . Transforming growth factor-beta1 down-regulation of major histocompatibility complex class Ⅰ in thyrocytes: coordinate regulation of two separate elements by thyroid-specific as well as ubiquitous transcription factors [J ] . Mol Endocrinol , 2000 , 14 ( 4 ): 486 - 505 .

SUZUKI K , LAVARONI S , MORI A , et al . Autoregulation of thyroid-specific gene transcription by thyroglobulin [J ] . Proc Natl Acad Sci U S A , 1998 , 95 ( 14 ): 8251 - 8256 .

杨燕君 , 张晓丽 , 董跃华 , 等 . 血清甲状腺转录因子1水平对表皮生长因子受体酪氨酸激酶抑制剂治疗肺腺癌效果的评估价值 [J ] . 中国医药 , 2020 , 15 ( 9 ): 1372 - 1376 .

YANG Y J , ZHANG X L , DONG Y H , et al . Value of serum thyroid transcription factor-1 level in evaluating the efficacy of epdermal growth factor receptor-tyrosine kinase inhibitors treatment lung adenocarcinoma [J ] . Chin Med , 2020 , 15 ( 9 ): 1372 - 1376 .

李笑 , 万里燕 , 申洪 , 等 . 血清甲状腺转录因子-1蛋白的变化特点及在肺癌诊断中的意义分析 [J ] . 南方医科大学学报 , 2011 , 31 ( 9 ): 1592 - 1596 .

LI X , WAN L Y , SHEN H , et al . Variation of serum thyroid transcription factor-1 protein and its value in the diagnosis of lung carcinoma [J ] . J South Med Univ , 2011 , 31 ( 9 ): 1592 - 1596 .

王静 . 胃癌患者血清FOXO4和甲状腺转录因子1水平及其临床意义 [J ] . 实用癌症杂志 , 2017 , 32 ( 5 ): 710 - 712 .

WANG J . Serum levels of FOXO4 and thyroid transcription factor 1 in gastric cancer and its clinical significance [J ] . Pract J Cancer , 2017 , 32 ( 5 ): 710 - 712 .

TAN H , WANG S S , HUANG F F , et al . Association between breast cancer and thyroid cancer risk: a two-sample Mendelian randomization study [J ] . Front Endocrinol , 2023 , 14 : 1138149 .

YUAN S , KAR S , VITHAYATHIL M , et al . Causal associations of thyroid function and dysfunction with overall, breast and thyroid cancer: a two-sample Mendelian randomization study [J ] . Int J Cancer , 2020 , 147 ( 7 ): 1895 - 1903 . DOI: 10.1002/ijc.32988 http://doi.org/10.1002/ijc.32988

HALADA S , CASADO-MEDRANO V , BARAN J A , et al . Hormonal crosstalk between thyroid and breast cancer [J ] . Endocrinology , 2022 , 163 ( 7 ): bqac075 .

KANYILMAZ G , AKTAN M , KOC M , et al . Radiation-induced hypothyroidism in patients with breast cancer: a retrospective analysis of 243 cases [J ] . Med Dosim , 2017 , 42 ( 3 ): 190 - 196 . DOI: S0958-3947(17)30034-1 http://doi.org/S0958-3947(17)30034-1

HUANG H K , ROBERSON J , HOU W , et al . NTCP model for hypothyroidism after supraclavicular-directed radiation therapy for breast cancer [J ] . Radiother Oncol , 2021 , 154 : 87 - 92 . DOI: 10.1016/j.radonc.2020.09.003 http://doi.org/10.1016/j.radonc.2020.09.003

DIGKAS E , SMITH D R , WENNSTIG A K , et al . Incidence and risk factors of hypothyroidism after treatment for early breast cancer: a population-based cohort study [J ] . Breast Cancer Res Treat , 2024 , 204 ( 1 ): 79 - 87 .

BHANDARE N , KENNEDY L , MALYAPA R S , et al . Primary and central hypothyroidism after radiotherapy for head-and-neck tumors [J ] . Int J Radiat Oncol Biol Phys , 2007 , 68 ( 4 ): 1131 - 1139 .

THOMAS O , MAHÉ M , CAMPION L , et al . Long-term complications of total body irradiation in adults [J ] . Int J Radiat Oncol Biol Phys , 2001 , 49 ( 1 ): 125 - 131 .

Views

1171

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Guidelines for breast cancer diagnosis and treatment by China Anti-Cancer Association (2026 edition)

Progress and prospects of CENPA-driven chromosomal instability in breast cancer: mechanisms, prognostic implications, and therapeutic perspectives

A study of 30-year trends in incidence and mortality risks of breast cancer among young women in China

Impact of miR-193a-3p on migration and invasion of breast cancer stem cells through targeting TRIM14

Axillary management after neoadjuvant therapy for breast cancer and optimization of sentinel lymph node diagnosis and treatment

Related Author

The Society of Breast Cancer China Anti-Cancer Association

Breast Oncology Group of the Oncology Branch of the Chinese Medical Association

LU Ye

ZHANG Wenxiang

KONG Xiangyi

FANG Yi

WANG Jing

GAO Jidong

Related Institution

Department of Breast Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

Department of Breast Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital& Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

Department of Cancer Prevention, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University

Shanghai Engineering Research Center of Artificial Intelligence Technology for Tumor Diseases

Department of Laboratory Medicine, Xingtai People’s Hospital

AI问答

⁰