ESRP1 as a prognostic factor of non-small-cell lung cancer is related to the EMT transcription factor of Twist.
ESRP1 as a prognostic factor of non-small-cell lung cancer is related to the EMT transcription factor of Twist.
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ESRP1作为非小细胞肺癌的预后因子与Twist的EMT转录因子相关
DOI：
10.1111/1759-7714.14088
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发表时间：
2021-09
期刊：
影响因子：
2.9
通讯作者：
Chen J
中科院分区：
文献类型：
--
作者：
Cui J;Ren P;Li Y;Ma Y;Wang J;Lin C;Jing L;Tong X;Ma S;Chen J
非小细胞肺癌（NSCLC）是世界上最常见的致命癌症之一。尽管NSCLC的治疗已得到显著改善，但仍存在未满足的需求，以鉴定用于开发治疗剂和诊断/预后标志物的新靶标。本研究旨在探讨上皮剪接调节蛋白1（ESRP 1）在非小细胞肺癌发生发展中的作用及其机制。共有115名参与者，65例NSCLC，20例癌前病变和30例良性肺结节，被纳入本研究。采用组织化学和免疫组化方法检测ESRP 1及其相关转录因子Twist在肺组织中的表达。采用Kaplan-Meier曲线和考克斯回归分析生存分析及影响预后的相关因素。此外，通过免疫组织化学和免疫印迹分析，在暴露于转化生长因子β1（TGFβ1）的A549肺腺癌细胞系上确定ESRP 1和上皮间质转化（EMT）相关转录因子Twist以及EMT标记物E-钙粘蛋白和N-钙粘蛋白的表达。与正常肺组织相比，癌前病变和肺癌组织中ESRP 1蛋白的丰度显著增加。相关分析显示ESRP 1是NSCLC的独立预后因素。ESRP 1与Twist在肺组织中的表达呈正相关（r = 0.285，p < 0.001）。体外实验进一步显示TGFβ1可上调EMT转录因子Twist的表达，下调ESRP 1的表达。我们的数据表明ESRP 1的异常表达是NSCLC发展的早期事件。ESRP 1可以作为NSCLC的预后生物标志物，特别是当与Twist联合使用时。Twist对ESRP 1表达有负调控作用，提示TGFβ/ESRP 1通路在NSCLC发生发展中的作用值得进一步研究。研究流程：共纳入115例肺组织标本，其中良性病变30例，癌前病变20例，非小细胞肺癌病变65例。
Non‐small‐cell lung cancer (NSCLC) is one of the most common fatal cancers in the world. Although the treatment of NSCLC has been significantly improved, there is still an unmet need to identify novel targets for developing therapeutic agents and diagnostic/prognostic markers. The aim of this study is explore the role and underlying mechanism of the epithelial splicing regulatory protein (ESRP1) in the development and progression of NSCLC. A total of 115 participants, 65 cases of NSCLC, 20 cases of precancerous lesions, and 30 cases of benign lung nodules, were included in this study. The expressions of ESRP1 and related transcription factor Twist in enrolled lung tissues were evaluated by histochemistry and immunohistochemistry assay. The survival analysis and related prognosis factors were evaluated by the Kaplan–Meier curve and Cox regression. In addition, the expression of ESRP1 and epithelial‐mesenchymal transition (EMT)related transcription factor Twist and EMT markers E‐cadherin and N‐cadherin were ascertained by immunohistochemical and immunoblotting assay on A549 lung adenocarcinoma cell lines that were exposed to transforming growth factor β1 (TGFβ1). Compared with normal lung tissues, the abundance of ESRP1 protein was significantly increased in precancerous lesions and lung cancer. Correlation analysis demonstrated that ESRP1 was an independent prognostic factor in NSCLC. The expression of ESRP1 and Twist was positively correlated in lung tissues (r = 0.285, p < 0.001). In vitro analysis further showed that TGFβ1 could upregulate the expression of EMT transcription factor Twist while downregulating ESRP1. Our data suggest that the aberrant expression of ESRP1 is an early event in the development of NSCLC. The ESRP1 could serve as a prognostic biomarker for NSCLC, particularly when combined with Twist. The Twist negatively regulated the expression of ESRP1, emphasizing the role of the TGFβ/ESRP1 pathway in the development of NSCLC, which warrants further investigation. Study flowchat: A total 115 samples of lung tissues were inclued in study, which including 30 cases of benign samples, 20 cases of precancerous lesions and 65 cases of NSCLC lesions for further study.
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影响因子：
4.1
作者：
Warzecha CC;Shen S;Xing Y;Carstens RP
通讯作者：
Carstens RP
SET8促进上皮间质转化并赋予TWIST双重转录活性
影响因子：
11.4
作者：
Yang, Fen;Sun, Luyang;Shang, Yongfeng
通讯作者：
Shang, Yongfeng
影响因子：
64.5
作者：
Yang, J;Mani, SA;Weinberg, RA
通讯作者：
Weinberg, RA
影响因子：
4.8
作者：
Reinke, Lauren M.;Xu, Yilin;Cheng, Chonghui
通讯作者：
Cheng, Chonghui
影响因子：
10
作者：
Walters, Sarah;Maringe, Camille;Rachet, Bernard
通讯作者：
Rachet, Bernard