The analysis of CCND1 amplification in Chinese patients with esophageal carcinoma.

Abstract

e16073 Background: The CCND1 gene is considered an oncogene located on human chromosome 11q13.3, Cyclin D1 protein encoded by the CCND1 gene is the critical gatekeeping protein in charge of regulating the transition. Previous studies have reported that CCND1 amplification associated with a negative response to immune checkpoint inhibitors (ICIs) in pancancers, but the association with clinical and molecular characteristics in esophageal carcinoma (ESCA) have not been researched. Herein, we explore CCND1 amplification profiles in Chinese patients with ESCA. Methods: A total of 59 patients of ESCA with paired tumor-normal samples were collected into the study. All samples were detected by DNA based sequencing with a 1021 gene panel. Results: Firstly, the frequency of CCND1 amplification in Chinese ESCA patients was 32.20% (19/59). Then, all the samples were divided into two groups according to whether CCND1 was amplified or not. In the CCND1 amplification group, the top8 co-mutated genes were TP53, FGF4, FGF3, FGF19, MYC, NOTCH1, CDKN2A, CDKN2B. We calculated the clinical and molecular characteristics between the two groups, the results showed there were no difference in gender, age and TNM stage. Meanwhile, the CCND1 amplification group had more somatic mutations (median 19 vs. 11, P = 0.0003), higher TMB value (median 8.64 vs. 5.76, P = 0.0199) and more TMB-H patients (47.37% vs. 17.50%, P = 0.018). Indicating the CCND1 amplification is associated with TMB-H in ESCA. However, previous studies have reported the negative impact of CCND1 amplification on the efficacy of ICIs in pancancer (including ESCA), these results suggesting the efficacy of ICIs in ESCA may be affected by multiple biomarkers, especially for TMB-H patients should be concerned about the high frequency CCND1 amplification, the patients may have a poorer benefit from immunotherapy. Conclusions: The efficacy of ICIs in ESCA may be affected by multiple biomarkers, especially for TMB-H patients should be concerned about the higher frequency of CCND1 amplification, these patients may have a poorer benefit from immunotherapy.[Table: see text]