Affiliation:
1. Department of Thoracic Surgery The First Affiliated Hospital of Anhui Medical University Hefei Anhui China
2. Jiangsu Simcere Diagnostics Co., Ltd., Nanjing Simcere Medical Laboratory Science Co., Ltd. The State Key Lab of Translational Medicine and Innovative Drug Development Nanjing China
3. Department of Biological Sciences Xi'an Jiaotong‐Liverpool University Suzhou China
Abstract
AbstractBackgroundThe molecular and immunological characteristics of primary tumors and positive lymph nodes in esophageal squamous cell carcinoma (ESCC) are unknown and the relationship with recurrence is unclear, which this study attempted to explore.MethodsA total of 30 ESCC patients with lymph node positive (IIB‐IVA) were enrolled. Among them, primary tumor and lymph node specimens were collected from each patient, and subjected to 551‐tumor‐targeted DNA sequencing and 289‐immuno‐oncology RNA panel sequencing to identify the different molecular basis and immunological features, respectively.ResultsThe primary tumors exhibited a higher mutation burden than lymph nodes (p < 0.001). One‐year recurrent ESCC exhibited a higher Mucin16 (MUC16) mutation rate (p = 0.038), as well as univariate and multivariate analysis revealed that MUC16 mutation is independent genetic factor associated with reduced relapse‐free survival (univariate, HR: 5.39, 95% CI: 1.67–17.4, p = 0.005; multivariate, HR: 7.36, 95% CI: 1.79–30.23, p = 0.006). Transcriptomic results showed non‐relapse group had higher cytolytic activity (CYT) score (p = 0.025), and was enriched in the IFN‐α pathway (p = 0.036), while those in the relapsed group were enriched in the TNF‐α/NF‐κB (p = 0.001) and PI3K/Akt pathway (p = 0.014).ConclusionThe difference in molecular characteristics between primary lesions and lymph nodes may be the cause of the inconsistent clinical outcomes. Mutations of MUC16 and poor immune infiltration are associated with rapid relapse of nodes‐positive ESCC.