A Novel Three-Gene Model Predicts Prognosis and Therapeutic Sensitivity in Esophageal Squamous Cell Carcinoma

Abstract

To precisely predict the clinical outcome and determine the optimal treatment options for patients with esophageal squamous cell carcinoma (ESCC) remains challenging. Prognostic models based on multiple molecular markers of tumors have been shown to have superiority over the use of single biomarkers. Our previous studies have identified the crucial role of ezrin in ESCC progression, which prompted us to hypothesize that ezrin-associated proteins contribute to the pathobiology of ESCC. Herein, we explored the clinical value of a molecular model constructed based on ezrin-associated proteins in ESCC patients. We revealed that the ezrin-associated proteins (MYC, PDIA3, and ITGA5B1) correlated with the overall survival (OS) and disease-free survival (DFS) of patients with ESCC. High expression of MYC was associated with advanced pTNM-stage (P=0.011), and PDIA3 and ITGA5B1 were correlated with both lymph node metastasis (PDIA3: P<0.001; ITGA5B1: P=0.001) and pTNM-stage (PDIA3: P=0.001; ITGA5B1: P=0.009). Furthermore, we found that, compared with the current TNM staging system, the molecular model elicited from the expression of MYC, PDIA3, and ITGA5B1 shows higher accuracy in predicting OS (P<0.001) or DFS (P<0.001) in ESCC patients. Moreover, ROC and regression analysis demonstrated that this model was an independent predictor for OS and DFS, which could also help determine a subgroup of ESCC patients that may benefit from chemoradiotherapy. In conclusion, our study has identified a novel molecular prognosis model, which may serve as a complement for current clinical risk stratification approaches and provide potential therapeutic targets for ESCC treatment.

Protein disulfide isomerase A3 as novel biomarker for endometrial cancer

“…Furthermore, our research demonstrated that PDIA3 had good prognostic value in EC patients. This finding is consistent with previous studies on esophageal squamous cell carcinoma ( 19 ), but contrary to the results reported in hepatocellular carcinoma ( 20 ). We attribute this discrepancy to the possibility of tumor heterogeneity, as the same gene may exhibit distinct functions in various diseases.…”

ATPase H+ Transporting V0 Subunit C regulates Twinfilin Actin Binding Protein 1 and promotes metastatic ability of esophageal cancer

“…At present, clinically targeted tumors such as esophageal cancer still lack very effective molecular diagnostic markers. At the same time, in addition to traditional surgery plus radiotherapy and chemotherapy, the application of gene therapy has been very poor [17,18]. Fundamentally speaking, the main reason for this situation is the lack of clinical research on target genes.…”

Interception of Signaling Circuits of Esophageal Adenocarcinoma Cells by Resveratrol Reveals Molecular and Immunomodulatory Signatures

“…Anterior gradient protein 2 homolog belongs to the protein disulfide isomerase family [ 51 ]. One of the proteins in the family of disulfide isomerase, termed PDIA3, is considered as a prognostic marker in esophageal cancer and also in other cancers, such as gastric cancer [ 52 , 53 ]; the survival prospect is favorable when the PDIA3 level was high when compared to when it was low. Additionally, protein disulfide isomerases are known to control key regulatory processes in a cell.…”