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EI2BL 的过表达通过诱导细胞 EMT 表型促进人非小细胞肺癌的进展。

Overexpression of EI2BL promoted human non-small cell lung cancer progression by inducing cell EMT phenotype.

机构信息

Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai, China.

Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.

出版信息

J Clin Pathol. 2020 Mar;73(3):139-146. doi: 10.1136/jclinpath-2019-205778. Epub 2019 Oct 5.

Abstract

AIMS

To unveil the role of EI2BL in non-small cell lung cancer (NSCLC) and the relationship between expression of EI2BL and the prognosis of patients with NSCLC.

METHODS

Immunohistochemistry (IHC), western blot analysis, immunofluorescence and real-time quantitative PCR (RT-qPCR) were used to evaluate EI2BL protein and mRNA levels in NSCLC and corresponding peritumour tissues. Cell Counting Kit-8, transwell assay and wound healing assay were used to analyse the abilities of cell proliferation, invasion and migration. In addition, the analysis of epithelial-mesenchymal transition (EMT) markers was also assessed by western blot analysis, RT-qPCR and immunofluorescence. Tissue micro-array analysis of 200 NSCLC cases was used to assess the relationship between EI2BL expression and clinicopathological characteristics. Moreover, the prognostic role of EI2BL in 200 patients with NSCLC was evaluated by Cox regression models and Kaplan-Meier methods.

RESULTS

Elevated EI2BL expression was more common in NSCLC tissues than paired peritumour tissues in both mRNA and protein level. EI2BL promoted the proliferation, invasion and migration of NSCLC cells. In addition, aberrant EI2BL expression might modulate the expression of key molecules of EMT by ERK1/2 signal pathway. The expression of EI2BL was significantly associated with tumour stage, lymph node metastasis and tumour size. Moreover, higher expression of EI2BL in patients with NSCLC had a poor overall survival rate.

CONCLUSIONS

Our study illustrated that elevated expression of EI2BL promoted NSCLC cell proliferation, migration and invasion and EI2BL overexpression may be a reliable biomarker of poor prognosis.

摘要

目的

揭示 EI2BL 在非小细胞肺癌(NSCLC)中的作用,以及 EI2BL 表达与 NSCLC 患者预后之间的关系。

方法

采用免疫组织化学(IHC)、western blot 分析、免疫荧光和实时定量 PCR(RT-qPCR)检测 NSCLC 及相应癌旁组织中 EI2BL 蛋白和 mRNA 水平。细胞计数试剂盒-8(CCK-8)、Transwell 检测和划痕愈合实验分析细胞增殖、侵袭和迁移能力。此外,通过 western blot 分析、RT-qPCR 和免疫荧光评估上皮-间质转化(EMT)标志物的分析。采用 200 例 NSCLC 组织的组织微阵列分析评估 EI2BL 表达与临床病理特征的关系。此外,通过 Cox 回归模型和 Kaplan-Meier 方法评估 EI2BL 在 200 例 NSCLC 患者中的预后作用。

结果

EI2BL 在 NSCLC 组织中的表达在 mRNA 和蛋白水平均高于配对癌旁组织。EI2BL 促进了 NSCLC 细胞的增殖、侵袭和迁移。此外,异常的 EI2BL 表达可能通过 ERK1/2 信号通路调节 EMT 关键分子的表达。EI2BL 的表达与肿瘤分期、淋巴结转移和肿瘤大小显著相关。此外,NSCLC 患者中 EI2BL 表达水平较高的患者总生存率较低。

结论

本研究表明,EI2BL 的高表达促进了 NSCLC 细胞的增殖、迁移和侵袭,EI2BL 过表达可能是预后不良的可靠标志物。

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