申雪芳, 花 晴, 王 敬, et al. EMT-TFs are predictors in lung cancer diagnosis and prognosis[J]. China Oncology, 2020, 30(4): 284-292. DOI: 10.19401/j.cnki.1007-3639.2020.04.007.
背景与目的:上皮-间质转化诱导转录因子(epithelial-mesenchymal transition-inducing transcription factor,EMT-TF)可调节肿瘤增殖、转移和肿瘤干细胞活化,在肺癌远处转移和复发中起重要作用,拟通过公共数据库来分析EMT-TF用于肺癌早期诊断及治疗方面的前景。方法:应用Oncomine和GEPIA数据库分析EMT-TF在肺癌组织及正常组织间的表达差异,及其与肺癌肿瘤分期的相关性;随后,使用Kaplan-Meier Plotter分析EMT-TF表达量与肺癌预后的关系;最后,通过STRING和Mentha数据库分析EMT-TF间的蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络及与之相互作用的分子。结果:肺癌组织Twist家族BHLH转录因子1(Twist family BHLH transcription factor 1,Twist1)表达明显增加,且其表达量越高,肺癌病理分期越重、预后越差;锌指E盒同源结合蛋白1(zinc finger E-box binding homeobox 1,ZEB1)和ZEB2在肺腺癌和肺鳞癌中表达降低,并与预后不良密切相关;Snail超家族锌指转录因子2(Snail family zinc finger 2)在肺癌中的表达水平增加,和肺癌临床分期具有明显相关性,但和肺癌的预后没有相关性。结论:Twist1、SNAI2、ZEB1和ZEB2在肺癌中的表达量和正常组织不同,Twist1和SNAI2的表达量与肿瘤的分期及预后相关,ZEB1和ZEB2在肺癌中表达量降低与肺癌患者的预后不良相关。因此,Twist1和SNAI2可能是肺癌诊断和研究潜在的生物标志物,ZEB1和ZEB2可作为肺癌预后的预测分子。
Abstract
Background and purpose: Epithelial-mesenchymal transition-inducing transcription factors (EMT-TFs) can regulate tumor proliferation
metastasis and tumor stem cell activation
and play an important role in distant metastasis and recurrence of lung cancer. This study intended to analyze the prospect of EMT-TFs in early diagnosis and treatment of lung cancer through public database. Methods: ONCOMINE and GEPIA databases were used to analyze the expression difference in EMT-TFs between lung cancer and normal tissues
and the correlation between EMT-TFs expression and tumor stage of lung cancer. Then
Kaplan Meier plotter tools were used to analyze the relationship between EMT-TFs expression and prognosis of lung cancer. Finally
STRING and Mentha: the interactome browser were used to analyze the protein-protein interaction (PPI) network between EMT-TFs and the molecules interacting with them. Results: The expression of Twist1 in lung cancer increased significantly
and the higher the expression
the poorer the pathological stage and prognosis of lung cancer were. The expression levels of zinc finger E-box binding homeobox 1 (ZEB1) and ZEB2 in lung adenocarcinoma and squamous cell carcinoma decreased
and were closely related to the poor prognosis. The increased transcription level of Snail family zinc finger 2 (SNAI2) in lung cancer was significantly related to the clinical stage of lung cancer
while it was not related to the prognosis of lung cancer. Conclusion: The expression levels of Twist1
SNAI2
ZEB1 and ZEB2 in lung cancer and normal tissues were different
and the expression levels of Twist1 and SNAI2 were related to tumor stage and prognosis
while low expressions of ZEB1/2 were associated with poor prognosis. Therefore
Twist1 may be a potential biomarker for the diagnosis and research of lung cancer
while ZEB1 or ZEB2 can be used as a predictor of the prognosis of lung cancer.