ERBB3在甲状腺癌患者中的表达及其意义

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摘要目的探讨ERBB3在甲状腺癌发生发展过程中的功能和作用。方法收集2017年12月～2018年12月北京潞河医院内分泌科甲状腺癌患者4例与甲状腺结节患者6例的细针穿刺组织进行RNA-seq检测，并分析ERBB3水平；利用TCGA甲状腺癌数据库与GEO甲状腺癌数据库，分析比较癌与癌旁，T、N分期，复发患者中ERBB3的水平；采用基因富集分析GSEA分析ERBB3水平与EGFR、PI3K、ERK1/2信号通路的关系，以及肿瘤增殖、转移的关系。结果与良性甲状腺结节比较，ERBB3 mRNA在甲状腺癌中表达量升高（P ＜ 0.001）。与癌旁比较，ERBB3 mRNA在甲状腺癌组织中升高（TCGA来源：P ＜ 0.0001；GEO来源：P ＜ 0.0001）。在甲状腺癌患者中，EGFR、PI3K、ERK1/2基因集显著富集于ERBB3高表达患者中。随着T分期的增长，ERBB3水平逐渐增加（P ＜ 0.0001）；与增殖相关的基因集显著富集于ERBB3高表达患者中。与N0组比较，N1期患者ERBB3水平显著增加（P ＜ 0.0001）。与转移相关的基因集显著富集于ERBB3高表达患者中。甲状腺癌复发患者ERBB3的水平升高（P = 0.0124）。结论 ERBB3可能参与了甲状腺癌的增殖、转移及复发，有望成为甲状腺癌治疗的新靶点。

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	王岩* 杨龙艳* 孙荣欣张媛媛付颖赵冬▲

关键词 ： ERBB3, 甲状腺癌, 增殖, 转移, 复发

Abstract：To investigate the effect and function of ERBB3 in the occurrence and development of thyroid cancer at clinical level. Methods The fine needle puncture tissues of 4 patients with thyroid cancer and 6 patients with thyroid nodule in Department of Endocrinology, Beijing Luhe Hospital from December 2017 to December 2018 were collected, RNA-seq was detected and ERBB3 levels were analyzed. The thyroid cancer database of TCGA and the thyroid cancer database of GEO were used to analyze and compare the levels of ERBB3 in patients with recurrent and paracancer, T and N stages. Gene enrichment analysis was used to analyze the relationship between ERBB3 level and EGFR, PI3K and ERK1/2 signaling pathways, as well as the relationship between tumor proliferation and metastasis. Results ERBB3 mRNA was increased in thyroid cancer compared with benign thyroid nodules (P ＜ 0.001). Compared with paracancer, ERBB3 mRNA was elevated in thyroid cancer tissues (TCGA source, P ＜ 0.0001; GEO source, P ＜ 0.0001). In thyroid cancer patients, EGFR, PI3K and ERK1/2 gene sets were significantly enriched in patients with high ERBB3 expression. ERBB3 levels increased with the increase of T staging (P ＜ 0.0001), and the gene sets associated with proliferation were significantly enriched in patients with high ERBB3 expression. Compared with the N0 group, the level of ERBB3 in patients with stage N1 was significantly increased (P ＜ 0.0001). The gene sets associated with metastasis were significantly enriched in patients with high ERBB3 expression. ERBB3 levels were elevated in patients with recurrent thyroid cancer (P = 0.0124). Conclusion ERBB3 may be involved in the proliferation, metastasis and recurrence of thyroid cancer and is expected to be a new target for the treatment of thyroid cancer.

Key words： ERBB3 Thyroid cancer Proliferation Metastasis Recurrence

基金资助:北京市通州区科学技术委员会国家自然科学基金攻坚专项课题（KJ2019CX014-06）。

通讯作者: ▲通讯作者

作者简介: 王岩（1991.10-），女，硕士；研究方向：甲状腺癌及糖脂代谢。杨龙艳（1983.2-），女，博士；研究方向：甲状腺癌及糖脂代谢。 *共同第一作者

引用本文:

王岩* 杨龙艳* 孙荣欣张媛媛付颖赵冬▲. ERBB3在甲状腺癌患者中的表达及其意义[J]. 中国医药导报, 2020, 17(5): 18-22.
WANG Yan* YANG Longyan* SUN Rongxin ZHANG Yuanyuan FU Ying ZHAO Dong▲. ERBB3 expression in thyroid cancer and its significance. 中国医药导报, 2020, 17(5): 18-22.

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