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.
Highlights
Esophageal cancer is the sixth leading cause of cancer-related deaths and the eighth most common type of malignant gastrointestinal cancer in the world [1, 2]
Low-expression of PDIA3 or high expression of ITGA5B1 significantly correlated with lymph node (LN) metastasis, whereas no correlation was found between molecules were significantly associated with OS (MYC) and LN metastasis (Table 2)
PDIA3 had a negative correlation while MYC and ITGA5B1 had a positive correlation with pTNM-stage (Table 2)
Summary
Esophageal cancer is the sixth leading cause of cancer-related deaths and the eighth most common type of malignant gastrointestinal cancer in the world [1, 2]. Adenocarcinoma and squamous cell carcinoma (ESCC) are the two major types of esophageal cancer, with the latter accounting for the 90% of cases worldwide [3]. In China, ESCC still remains the highest incidence and cancer-induced mortality rates, and the long-term prognosis of patients with ESCC is less than 20%, despite improvements in treatments such as surgical resection and adjuvant chemoradiation [4, 5]. BioMed Research International identify patients at high risk and improving their prognosis are urgent needs in the clinic. Signal molecular marker cannot meet the clinical requirements for biomarkers, such as high sensitivity and specificity, and it is more accurate than the current clinical staging system [7]. In the last few years, studies have demonstrated that combinations of multiple biomarkers were more sensitive and reliable than single molecular marker. Several prognostic biomarkers for ESCC have been reported [8,9,10,11,12], there is still no ideal biomarker for clinical use
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