Chen Zui, Che Di, Gu Xiaoqiong, Lin Jiamin, Deng Jing, Jiang Ping, Xu Kaixiong, Xu Banglao, Zhang Ting
Department of Laboratory Medicine, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China.
Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Front Oncol. 2021 Feb 26;11:625612. doi: 10.3389/fonc.2021.625612. eCollection 2021.
Invasion and metastasis represent the primary causes of therapeutic failure in patients diagnosed with esophageal squamous cell carcinoma (ESCC). The lack of effective treatment strategies for metastatic ESCC is the major cause of the low survival rate. Therefore, it is crucial to understand the molecular mechanisms underlying ESCC metastasis and identify potential biomarkers for targeted therapy. Herein, we reported that PEDF is significantly correlated with tumor cell invasion and metastasis in ESCC. The high expression of PEDF is an independent unfavorable prognostic factor for ESCC patients' overall survival (OS). We successfully developed and verified a nomogram to predict the preoperative OS of ESCC patients, and the actual and nomogram-predicted 1-, 3-, and 5-year survival rates had good consistency. The receiver operating characteristic (ROC) curve showed that the area under the curve (AUC) values for 1-, 3- and 5- survival were 0.764, 0.871, and 0.91, respectively. Overexpression of PEDF significantly promoted the migration and invasion of ESCC cells , while silencing PEDF yielded the opposite effects. Elevated levels of PEDF altered the expression of proteins involved in epithelial-mesenchymal transition (EMT), as indicated by the upregulation of N-cadherin and the downregulation of -catenin and E-cadherin in ESCC cells. Mechanistically, PEDF promoted tumor cell motility and EMT by activating the MAPK/ERK signaling pathway. In conclusion, our results reveal that PEDF is involved in ESCC metastasis and could act as a prognostic factor for ESCC. Our research provides a fresh perspective into the mechanism of ESCC metastasis.
侵袭和转移是导致食管鳞状细胞癌（ESCC）患者治疗失败的主要原因。转移性ESCC缺乏有效的治疗策略是生存率低的主要原因。因此，了解ESCC转移的分子机制并确定潜在的靶向治疗生物标志物至关重要。在此，我们报告PEDF与ESCC中的肿瘤细胞侵袭和转移显著相关。PEDF的高表达是ESCC患者总生存期（OS）的一个独立不良预后因素。我们成功开发并验证了一种列线图来预测ESCC患者的术前OS，实际生存率与列线图预测的1年、3年和5年生存率具有良好的一致性。受试者工作特征（ROC）曲线显示，1年、3年和5年生存率的曲线下面积（AUC）值分别为0.764、0.871和0.91。PEDF的过表达显著促进了ESCC细胞的迁移和侵袭，而沉默PEDF则产生相反的效果。ESCC细胞中PEDF水平升高改变了参与上皮-间质转化（EMT）的蛋白质表达，表现为N-钙黏蛋白上调以及β-连环蛋白和E-钙黏蛋白下调。机制上，PEDF通过激活MAPK/ERK信号通路促进肿瘤细胞运动性和EMT。总之，我们的结果表明PEDF参与ESCC转移，并可作为ESCC的一个预后因素。我们的研究为ESCC转移机制提供了新的视角。
