Abstract
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 in vitro, 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 α-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.
Highlights
Esophageal carcinoma ranked sixth among the causes of cancerrelated death globally in 2018, and its incidence has rapidly increased in recent decades
In our study of the reliability of the analysis, we found that the expression of only 111 genes was consistent between the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases
We found that the expression of Pigment epithelium-derived factor (PEDF) in esophageal carcinoma was different from that in other cancers and that the expression of PEDF in esophageal cancer precursor samples was lower than that in esophageal carcinoma samples (Figures 1D and S1A)
Summary
Esophageal carcinoma ranked sixth among the causes of cancerrelated death globally in 2018, and its incidence has rapidly increased in recent decades. The prevalence and mortality rate of esophageal carcinoma in China rank fifth worldwide, but China accounts for approximately half of all new cases and deaths [1, 2]. There are two main forms of esophageal carcinoma: adenocarcinoma and squamous cell carcinoma. Esophageal squamous cell carcinoma (ESCC) is the most common histologic type of esophageal cancer worldwide. The prognosis of ESCC patients is generally poor and is dependent on the existence of metastases [4, 5]. Therapeutic approaches are most likely dependent on the existence of tumor metastases, the genetic composition and the tumor subtype [6]. More detailed works in the future need to effectively explore the mechanism of ESCC at the molecular level and develop improved diagnostic and therapeutic agents
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