[关键词]
[摘要]
目的:分析FOXD1 在食管鳞状细胞癌(ESCC)组织中的表达及其与临床病理特征和患者预后的关系,探讨其对 ESCC TE1 细胞增殖、侵袭能力的影响及其对TGF-β1 诱导TE1 细胞EMT 进程的影响。方法:采用qPCR 和IHC 法检测ESCC 组 织和细胞中FOXD1 的表达,并分析其与临床病理特征和患者预后的关系;构建FOXD1 敲减质粒并转染TE1 细胞,检测其对TE1 细胞增殖、侵袭能力的影响;用qPCR 和WB 法检测TGF-β1 处理前后FOXD1 及EMT 相关基因和蛋白的表达变化及敲减FOXD1 对EMT 相关基因和蛋白表达的影响。结果:ESCC 组织和细胞中FOXD1 均呈高表达(均P<0.01),并与患者OS 呈负相关;FOXD1 表达水平、肿瘤TNM 分期以及淋巴结转移均是影响ESCC 患者预后的独立危险因素(均P<0.01)。TGF- β1 可促进TE1 细胞FOXD1 的表达,并诱发其EMT 进程(均P<0.05);敲减FOXD1 可抑制TE1 细胞的增殖和侵袭能力,并可部分逆转由TGF-β1 诱发的TE1 细胞EMT 进程。结论:FOXD1 在ESCC 组织及TE1 细胞中呈高表达且是影响ESCC 患者预后的独立危险因素,敲低 FOXD1 可显著抑制TE1 细胞的增殖、侵袭及TGF-β1 介导的EMT 进程。
[Key word]
[Abstract]
Objective: To analyze the expression of FOXD1 in esophageal squamous cell carcinoma (ESCC) and its relationship with clinicopathological features and prognosis. To investigate the effect of FOXD1 on the proliferation and invasion of TE1 cells and its effect on TGF- β1 induction of epithelial-mesenchymal transition (EMT). Methods: The expression of FOXD1 in ESCC tissues and cells was detected by qPCR and immunohistochemical method (IHC). The relationships between its expression level and clinicopathological characteristics and prognosis of patients were also analyzed. FOXD1 knockdown plasmid was constructed and transfected into TE1 cells to detect its effect on the proliferation and invasion of TE1 cells. qPCR and Western blotting were used to detect the expression levels of FOXD1 and EMT-related markers before and after TGF- β1 treatment and the effect of knockdown FOXD1 on the expression of EMT-related markers. Results: FOXD1 was highly expressed in ESCC tissues and cells (all P<0.01), and negatively correlated with the overall survival of patients. FOXD1 expression level, tumor TNM stage, and lymph node metastasis were independent factors affecting the prognosis of ESCC patients (all P<0.01). TGF-β1 treatment may raise the expression level of FOXD1 in TE1 cells and induce the expression of EMT-related markers (all P<0.05). Knockdown FOXD1 may suppress the proliferation and invasion ability of TE1 cells and can partially reverse the EMT process of TE1 cells induced by TGF-β1. Conclusion: FOXD1, highly expressed in ESCC tissues and TE1 cells, is an independent factor affecting the prognosis of ESCC patients. Knockdown of FOXD1 can significantly inhibit the proliferation, invasion and TGF-β1 mediated EMT process of TE1 cells.
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[基金项目]
河北省医学科学研究重点课题计划资助项目(No. 20220154)