FOXD1在食管鳞状细胞癌组织中表达的意义及其对TE1细胞恶性生物学行为影响的分子机制

Clinical significance of FOXD1 expression in esophageal squamous cell carcinoma and the mechanism of its effect on the malignant biological behaviors of TE1 cells

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。

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 FOXD1in 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 FOXD1can significantly inhibit the proliferation, invasion and TGF-β1 mediated EMT process of TE1 cells.