叉头框蛋白 D1 通过调控头颈部鳞状细胞癌细胞表皮生长因子受体的表达来调节西妥昔单抗敏感性。
FOXD1 Regulates the Sensitivity of Cetuximab by Regulating the Expression of EGFR in Head and Neck Squamous Cell Cancer.
机构信息
Department of Otorhinolaryngology Head and Neck Surgery, First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121000, China.
Communist Youth League Committee, First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121000, China.
出版信息
J Healthc Eng. 2022 Jan 25;2022:6108241. doi: 10.1155/2022/6108241. eCollection 2022.
OBJECTIVES
Previous experiments have shown that growth factor receptors play important role in tumor proliferation, metastasis, and therapeutic effect of chemotherapeutic drugs. At the same time, forkhead box D1 (FOXD1) plays an important role in a variety of signal transmission, but its expression profile was known little about head and neck cancer. The purpose of this experiment was to explore the regulation of FOXD1 on the tumor progression of head and neck cancer and to explore the correlation of FOXD1 on the expression of growth factor receptors (EGFR).
METHODS
The bioinformatics online database analyzed the expression of FOXD1 and EGFR in tumor tissues and nontumor tissues. Real-time quantitative PCR was used to detect the FOXD1 and EGFR expression in 45 tumor tissues and 15 nontumor tissues. The plasmid was used to construct FOXD1 overexpressing head and neck squamous cell cancer lines and observe the clonal formation and invasion of tumor cells under the intervention of EGFR-specific antibody-cetuximab.
RESULTS
The expression of FOXD1 and EGFR in tumor tissues was higher than that in nontumor tissues. The higher expression of FOXD1 and EGFR was not conducive to the prognosis of patients. The expression of FOXD1 and EGFR was positively correlated, and immunohistochemical analysis showed the high expression of FOXD1 and EGFR has close relation to the advanced stage of the tumor. In vitro cell experiments proved that overexpression of FOXD1 can partially offset the cloning ability of cetuximab on head and neck tumor cells.
CONCLUSION
FOXD1 has an important regulatory role in the progression of head and neck cancer, and its abnormally high expression was not conducive to the prognosis of cancer patients. FOXD1 can regulate the expression of growth factor receptors in head and neck cancer, which provides a new idea for the better use of tumor growth factor receptor-specific antibodies for collaborative therapy.
目的
先前的实验表明，生长因子受体在肿瘤增殖、转移以及化疗药物的治疗效果中发挥着重要作用。与此同时，叉头框蛋白 D1（FOXD1）在多种信号转导中发挥着重要作用，但关于其在头颈部肿瘤中的表达谱知之甚少。本实验旨在探讨 FOXD1 对头颈部癌症肿瘤进展的调控作用，并探讨 FOXD1 与生长因子受体（EGFR）表达的相关性。
方法
通过生物信息学在线数据库分析 FOXD1 和 EGFR 在肿瘤组织和非肿瘤组织中的表达情况。采用实时定量 PCR 检测 45 例肿瘤组织和 15 例非肿瘤组织中 FOXD1 和 EGFR 的表达情况。构建 FOXD1 过表达的头颈部鳞状细胞癌细胞系，并观察 EGFR 特异性抗体西妥昔单抗干预下肿瘤细胞的克隆形成和侵袭。
结果
肿瘤组织中 FOXD1 和 EGFR 的表达高于非肿瘤组织。FOXD1 和 EGFR 表达越高，患者的预后越差。FOXD1 和 EGFR 的表达呈正相关，免疫组化分析显示 FOXD1 和 EGFR 的高表达与肿瘤的晚期密切相关。体外细胞实验证明，FOXD1 的过表达可以部分抵消西妥昔单抗对头颈部肿瘤细胞的克隆能力。
结论
FOXD1 在头颈部癌症的进展中具有重要的调节作用，其异常高表达不利于癌症患者的预后。FOXD1 可以调节头颈部癌症中生长因子受体的表达，为更好地利用肿瘤生长因子受体特异性抗体进行协同治疗提供了新的思路。
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