1482P Comprehensive molecular profiling and identification of prognostic factors in patients with resectable esophageal squamous cell carcinoma

Abstract

Esophageal cancer is a serious malignancy with high rates of incidence and mortality. Almost half of the global esophageal cancers occur in China and the most prevalent type is esophageal squamous cell carcinoma (ESCC). However, the molecular signatures in resectable ESCC are not well elucidated. The aim of this study is to investigate the genetic profiles and explore prognostic indicators in patients with resectable ESCC. Patients diagnosed with primary ESCC (clinical stage I-III) who received surgery were enrolled. Tumor tissue samples were collected for next-generation sequencing (NGS) with Acornmed Panel (more than 2.0 megabase (Mb)) covering 808 cancer-related genes. A total of 55 resectable ESCC patients were enrolled in this study. Overall, 634 non-synonymous somatic variants from 270 genes were identified. The most commonly mutated genes in ESCC were TP53, CCND1, CDKN2A, NOTCH1, MLL2, PIK3CA and FAT1. Many tumors contained mutations in genes of epigenetic processes (EP300, KDM6A, MLL1, MLL2, RB1), and pairwise associations analysis showed that genomic alterations in the epigenetic processes tended to co-exist with alterations of other signaling pathways in ESCC. According to the clinical actionability to targetable alterations stratified by OncoKB classification system, the most common targets in ESCC were alterarions of CDKN2A, PIK3CA, EGFR and KDM6A. Moreover, the prognostic significance of the frequently mutated genes in ESCC was further investigated. The results showed that CCND1 and EP300 mutations were correlated with poor recurrence-free survival (CCND1: hazard ratio [HR], 2.83; 95% confidence interval [CI], 1.17-6.81; P = 0.006; EP300: HR, 2.73; 95% CI, 0.56-14.33; P = 0.043) and overall survival (CCND1: HR, 2.44; 95% CI, 0.96-6.21; P = 0.042; EP300: HR, 3.56; 95% CI, 0.61-20.80; P = 0.012). This study is of great significance in understanding the molecular characterization of resectable ESCC patients. The findings define the genomic profile and reveal prognostic indicators for ESCC, which will be helpful to guide personalized therapy and promote the clinical management of this population.