Effect of extracapsular lymph node involvement on the prognosis of patients with esophageal squamous cell carcinoma

BACKGROUND: According to the eighth edition of the tumor node metastasis (TNM) staging system for esophageal cancer, it is recommended that extracapsular lymph node involvement (EC-LNI) is included as a registered independent variable for the disease. However, its role in the prognosis has not been clearly explained. OBJECTIVE: To study the value of EC-LNI in the prognosis of esophageal cancer and attempt to explore its molecular mechanism via an enrichment analysis. METHODS: A retrospective analysis was performed on 544 patients with esophageal squamous cell carcinoma (ESCC) who underwent radical surgery in the department of thoracic surgery of our hospital, focusing on the relationship between EC-LNI and clinicopathological characteristics and its effect on prognosis. Additionally, the mechanism of EC-LNI in esophageal cancer was explored. RESULTS: Among the 271 patients with lymph node metastasis, 125 were EC-LNI (+). The degrees of tumor differentiation, location, TNM stage, vascular tumor thrombus, and nerve invasion were related to the occurrence of EC-LNI. The stage of TNM was considered an independent risk factor for the development of EC-LNI. A significant difference was found in terms of overall survival (OS) and disease-free survival (DFS) between the EC-LNI (+) and EC-LNI (-) groups. A univariate analysis showed that the degrees of tumor differentiation, T stage, N stage, TNM stage, EC-LNI, EC-LNI number, and EC-LNI distance were significantly correlated with prognosis. A multivariate survival analysis showed that tumor differentiation, TNM stage, and EC-LNI were independent prognostic factors for OS, while TNM stage and EC-LNI were independent prognostic factors for DFS. The enrichment analysis identified the molecular targets and signaling pathways that can regulate cell proliferation, differentiation, and apoptosis. CONCLUSION: Extracapsular LNI has a high prognostic value in patients with esophageal cancer and is closely related to the stage of tumors. Our preliminary molecular mechanism research indicated that the molecular targets of EC-LNI are expected to become a new direction for the treatment of esophageal cancer.