甲状腺激素水平与肾细胞癌及肝细胞癌多靶点TKI治疗疗效预测及其分子机制

国际肿瘤学杂志››2019,Vol. 46››Issue (5): 303-306.doi:10.3760/cma.j.issn.1673-422X.2019.05.011

甲状腺激素水平与肾细胞癌及肝细胞癌多靶点TKI治疗疗效预测及其分子机制

孙月琴，李爱民，罗越，宋争徽，庄雪芬，戴冠齐，刘新会

南方医科大学中西医结合医院肝胆胰肿瘤科，广州510315

收稿日期:2019-02-22出版日期:2019-05-08发布日期:2019-06-14
通讯作者:刘新会 E-mail:liuxinhui89@126.com
基金资助:

国家自然科学基金（81572797）；广东省自然科学基金（2016A030311015）；广州市科技计划（201604020009）

Efficacy prediction and molecular mechanism of thyroid hormone levels and multi-target TKI therapy for renal cell carcinoma and hepatocellular carcinoma

Sun Yueqin, Li Aimin, Luo Yue, Song Zhenghui, Zhuang Xuefen, Dai Guanqi, Liu Xinhui

Department of Hepatobiliary and Pancreatic Oncology, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510315, China

Received:2019-02-22Online:2019-05-08Published:2019-06-14
Contact:Liu Xinhui E-mail:liuxinhui89@126.com
Supported by:

National Natural Science Foundation of China (81572797); Natural Science Foundation of Guangdong Province of China (2016A030311015); Science and Technology Project of Guangzhou City of China (201604020009)

摘要/Abstract

摘要：甲状腺功能减退是临床多靶点酪氨酸激酶抑制剂（TKI）的常见不良反应，可能作为TKI药物的疗效预测指标。研究发现甲状腺功能减退与接受多靶点TKI治疗的肾细胞癌患者良好预后显著相关，这可能与血管内皮细胞生长因子受体通路阻滞、潜在脱靶作用和细胞增殖受抑制有关；而在接受多靶点TKI治疗的肝细胞癌患者中，甲状腺功能减退则是预后不良的指标，这与T3/TR通路调控肝癌生长侵袭相关。在接受多靶点TKI药物治疗的不同肿瘤患者中，甲状腺激素水平的疗效预测功能及机制并不相同，仍需进一步深入研究。

关键词:甲状腺激素类,肿瘤,预后,酪氨酸激酶抑制剂

Abstract:Hypothyroidism is a common adverse reaction in clinical multi-target tyrosine kinase inhibitor (TKI) and may be used as a predictor of efficacy of TKI drugs. Studies show that hypothyroidism is significantly associated with good prognosis in patients with renal cell carcinoma treated with multi-target TKI, which may be related to inhibition of vascular endothelial growth factor receptor pathway, potential offtarget effects and inhibition of cell proliferation. Whereas in the patients with hepatocellular carcinoma who received multi-target TKI therapy, hypothyroidism is an indicator of poor prognosis, which is related to the T3/TR pathway regulating liver cancer growth and invasion. The predictive function and mechanism of thyroid hormone levels in different tumor patients receiving multi-target TKI drugs are different, and further research is still needed.

Key words:Thyroid hormones,Neoplasms,Prognosis,Tyrosine kinase inhibitors

孙月琴，李爱民，罗越，宋争徽，庄雪芬，戴冠齐，刘新会. 甲状腺激素水平与肾细胞癌及肝细胞癌多靶点TKI治疗疗效预测及其分子机制[J]. 国际肿瘤学杂志, 2019, 46(5): 303-306.

Sun Yueqin, Li Aimin, Luo Yue, Song Zhenghui, Zhuang Xuefen, Dai Guanqi, Liu Xinhui. Efficacy prediction and molecular mechanism of thyroid hormone levels and multi-target TKI therapy for renal cell carcinoma and hepatocellular carcinoma[J]. Journal of International Oncology, 2019, 46(5): 303-306.

参考文献

［1］ Shi XZ, Jin X, Xu P, et al. Relationship between breast cancer and levels of serum thyroid hormones and antibodies: a metaanalysis［J］. Asian Pac J Cancer Prev, 2014, 15(16): 6643-6647. ［2］ Prinzi N, Sorrenti S, Baldini E, et al. Association of thyroid diseases with primary extrathyroidal malignancies in women: results of a cross-sectional study of 6,386 patients［J］. PLoS One, 2015, 10(3): e122958. DOI: 10.1371/journal.pone.0122958. ［3］ Pinter M, Haupt L, Hucke F, et al. The impact of thyroid hormones on patients with hepatocellular carcinoma［J］. PLoS One, 2017, 12(8): e0181878. DOI: 10.1371/journal.pone.0181878. ［4］ Borriello A, Caldarelli I, Bencivenga D, et al. Tyrosine kinase inhibitors and mesenchymal stromal cells: effects on selfrenewal, commitment and functions［J］. Oncotarget, 2017, 8(3): 5540-5565. DOI: 10.18632/oncotarget.12649. ［5］ Jiao Q, Bi L, Ren Y, et al. Advances in studies of tyrosine kinase inhibitors and their acquired resistance［J］. Mol Cancer, 2018, 17(1): 36. DOI: 10.1186/s12943-018-0801-5. ［6］ Qin S, Li A, Yi M, et al. Recent advances on antiangiogenesis receptor tyrosine kinase inhibitors in cancer therapy［J］. J Hematol Oncol, 2019, 12(1): 27. DOI: 10.1186/s13045-019-0718-5. ［7］ Beukhof CM, van Doorn L, Visser TJ, et al. Sorafenibinduced changes in thyroid hormone levels in patients treated for hepatocellular carcinoma［J］. J Clin Endocrinol Metab, 2017, 102(8): 2922-2929. DOI: 10.1210/jc.2016-4025. ［8］ Mondello P, Mian M, Pitini V, et al. Thyroid hormone autoantibodies: are they a better marker to detect early thyroid damage in patients with hematologic cancers receiving tyrosine kinase inhibitor or immunoregulatory drug treatments?［J］. Curr Oncol, 2016, 23(3): e165-e170. DOI: 10.3747/co.23.3026. ［9］ Motzer RJ, Jonasch E, Agarwal N, et al. Kidney cancer, version 2.2017, NCCN clinical practice guidelines in oncology［J］. J Natl Compr Canc Netw, 2017, 15(6): 804-834. DOI: 10.6004/jnccn.2017.0100. ［10］ Wolter P, Stefan C, Decallonne B, et al. Evaluation of thyroid dysfunction as a candidate surrogate marker for efficacy of sunitinib in patients with advanced renal cell cancer (RCC)［J］. J Clin Oncol, 2008, 26(15_Suppl): 5126. DOI: 10.1200/jco.2008.26.15_suppl.5126. ［11］ Riesenbeck LM, Bierer S, Hoffmeister I, et al. Hypothyroidism correlates with a better prognosis in metastatic renal cancer patients treated with sorafenib or sunitinib［J］. World J Urol, 2011, 29(6): 807-813. DOI: 10.1007/s00345-010-0627-2. ［12］ Nearchou A, Valachis A, Lind P, et al. Acquired hypothyroidism as a predictive marker of outcome in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors: a literature-based meta-analysis［J］. Clin Genitourin Cancer, 2015, 13(4): 280-286. DOI: 10.1016/j.clgc.2014.10.002. ［13］ Lechner MG, Vyas CM, Hamnvik OR, et al. Hypothyroidism during tyrosine kinase inhibitor therapy is associated with longer survival in patients with advanced nonthyroidal cancers［J］. Thyroid, 2018, 28(4): 445-453. DOI: 10.1089/thy.2017.0587. ［14］ Wang T, Xia L, Ma S, et al. Hepatocellular carcinoma: thyroid hormone promotes tumorigenicity through inducing cancer stem-like cell self renewal［J］. Sci Rep, 2016, 6: 25183. DOI: 10.1038/srep25183. ［15］ Zhang N, Jin W, Zhou S, et al. Hypothyroidism is associated with worse outcomes of hepatocellular carcinoma patients after liver transplantation［J］. Cancer Med, 2018, 7(12): 5870-5878. DOI: 10.1002/cam4.1797. ［16］ Chu YD, Lin KH, Huang YH, et al. A novel thyroid function index associated with opposite therapeutic outcomes in advanced hepatocellular carcinoma patients receiving chemotherapy or sorafenib［J］. Asia Pac J Clin Oncol, 2018, 14(5): e341-e351. DOI: 10.1111/ajco.12983. ［17］ BudaNowak A, Kucharz J, Dumnicka P, et al. Sunitinibinduced hypothyroidism predicts progressionfree survival in metastatic renal cell carcinoma patients［J］. Med Oncol, 2017, 34(4): 68. DOI: 10.1007/s12032-017-0928-z. ［18］ White PT, Cohen MS. The discovery and development of sorafenib for the treatment of thyroid cancer［J］. Expert Opin Drug Discov, 2015, 10(4): 427-439. DOI: 10.1517/17460441.2015.1006194. ［19］ De Falco V, Carlomagno F, Li HY, et al. The molecular basis for RET tyrosinekinase inhibitors in thyroid cancer［J］. Best Pract Res Clin Endocrinol Metab, 2017, 31(3): 307-318. DOI: 10.1016/j.beem.2017.04.013. ［20］ Drui D, Illouz F, Do Cao C, et al. Expert opinion on thyroid complications of new anticancer therapies: tyrosine kinase inhibitors［J］. Ann Endocrinol (Paris), 2018, 79(5): 569-573. DOI: 10.1016/j.ando.2018.07.003. ［21］ Shu M, Zai X, Zhang B, et al. Hypothyroidism side effect in patients treated with sunitinib or sorafenib: clinical and structural analyses［J］. PLoS One, 2016, 11(1): e0147048. DOI: 10.1371/journal.pone.0147048. ［22］ Lin HY, Chin YT, Yang YC, et al. Thyroid hormone, cancer, and apoptosis［J］. Compr Physiol, 2016, 6(3): 1221-1237. DOI: 10.1002/cphy.c150035. ［23］ Czarnecka AM, Matak D, Szymanski L, et al. Triiodothyronine regulates cell growth and survival in renal cell cancer［J］. Int J Oncol, 2016, 49(4): 1666-1678. DOI: 10.3892/ijo.2016.3668. ［24］ Frau C, Loi R, Petrelli A, et al. Local hypothyroidism favors the progression of preneoplastic lesions to hepatocellular carcinoma in rats［J］. Hepatology, 2015, 61(1): 249-259. DOI: 10.1002/hep.27399. ［25］ Perra A, Plateroti M, Columbano A. T3/TRs axis in hepatocellular carcinoma: new concepts for an old pair［J］. Endocr Relat Cancer, 2016, 23(8): R353-R369. DOI: 10.1530/ERC-16-0152. ［26］ MartinezIglesias O, GarciaSilva S, Tenbaum SP, et al. Thyroid hormone receptor beta1 acts as a potent suppressor of tumor invasiveness and metastasis［J］. Cancer Res, 2009, 69(2): 501-509. DOI: 10.1158/0008-5472.CAN-08-2198. ［27］ Chung IH, Chen CY, Lin YH, et al. Thyroid hormonemediated regulation of lipocalin 2 through the Met/FAK pathway in liver cancer［J］. Oncotarget, 2015, 6(17): 15050-15064. DOI: 10.18632/oncotarget.3670. ［28］ Wu SM, Cheng WL, Liao CJ, et al. Negative modulation of the epigenetic regulator, UHRF1, by thyroid hormone receptors suppresses liver cancer cell growth［J］. Int J Cancer, 2015, 137(1): 37-49. DOI: 10.1002/ijc.29368. ［29］ Hercbergs AA, Goyal LK, Suh JH, et al. Propylthiouracilinduced chemical hypothyroidism with high-dose tamoxifen prolongs survival in recurrent high grade glioma: a phase Ⅰ/Ⅱ study［J］. Anticancer Res, 2003, 23(1B): 617-626.

[1]	刘娜, 寇介丽, 杨枫, 刘桃桃, 李丹萍, 韩君蕊, 杨立洲.血清miR-106b-5p、miR-760联合低剂量螺旋CT诊断早期肺癌的临床价值[J]. 国际肿瘤学杂志, 2024, 51(6): 321-325.
[2]	钱晓涛, 石子宜, 胡格, 吴晓维.Ⅲ~ⅣA期食管鳞状细胞癌放化疗后行巩固化疗的疗效：一项真实世界临床研究[J]. 国际肿瘤学杂志, 2024, 51(6): 326-331.
[3]	杨蜜, 别俊, 张加勇, 邓佳秀, 唐组阁, 卢俊.局部晚期可切除食管癌新辅助治疗疗效及预后分析[J]. 国际肿瘤学杂志, 2024, 51(6): 332-337.
[4]	袁健, 黄燕华.Hp-IgG抗体联合血清DKK1、sB7-H3对早期胃癌的诊断价值[J]. 国际肿瘤学杂志, 2024, 51(6): 338-343.
[5]	陈红健, 张素青.血清miR-24-3p、H2AFX与肝癌患者临床病理特征及术后复发的关系研究[J]. 国际肿瘤学杂志, 2024, 51(6): 344-349.
[6]	郭泽浩, 张俊旺.PFDN及其亚基在肿瘤发生发展中的作用[J]. 国际肿瘤学杂志, 2024, 51(6): 350-353.
[7]	张百红, 岳红云.新作用机制的抗肿瘤药物进展[J]. 国际肿瘤学杂志, 2024, 51(6): 354-358.
[8]	许凤琳, 吴刚.EBV在鼻咽癌肿瘤免疫微环境和免疫治疗中的研究进展[J]. 国际肿瘤学杂志, 2024, 51(6): 359-363.
[9]	王盈, 刘楠, 郭兵.抗体药物偶联物在转移性乳腺癌治疗中的研究进展[J]. 国际肿瘤学杂志, 2024, 51(6): 364-369.
[10]	张蕊, 褚衍六.基于FIT与肠道菌群的结直肠癌风险评估模型的研究进展[J]. 国际肿瘤学杂志, 2024, 51(6): 370-375.
[11]	高凡, 王萍, 杜超, 褚衍六.肠道菌群与结直肠癌非手术治疗的相关研究进展[J]. 国际肿瘤学杂志, 2024, 51(6): 376-381.
[12]	王丽, 刘志华, 杨伟洪, 蒋凤莲, 李全泳, 宋浩杰, 鞠文东.ROS1突变肺腺鳞癌合并脑梗死为主要表现的Trousseau综合征1例[J]. 国际肿瘤学杂志, 2024, 51(6): 382-384.
[13]	范志鹏, 余静, 胡静, 廖正凯, 徐禹, 欧阳雯, 谢丛华.炎症标志物的变化趋势对一线接受免疫联合化疗的晚期非小细胞肺癌患者预后的预测价值[J]. 国际肿瘤学杂志, 2024, 51(5): 257-266.
[14]	刘静, 刘芹, 黄梅.基于SMOTE算法的食管癌放化疗患者肺部感染的预后模型构建[J]. 国际肿瘤学杂志, 2024, 51(5): 267-273.
[15]	杨琳, 路宁, 温华, 张明鑫, 朱琳.炎症负荷指数与胃癌临床关系研究[J]. 国际肿瘤学杂志, 2024, 51(5): 274-279.