Abstract 1497: Identification of discrepancy between CTLA4 expression and CTLA4 activation in gastric cancer

Abstract

Abstract Objective: Recently, immune checkpoints blockers showed higher anti-tumor activity for advanced gastric cancer (GC). The purpose of the study is to find out biomarkers related to anti-CTLA4 therapy. Materials and Methods: Datasets of GEO, TCGA and GESA were extracted. Differential expression of CTLA4 between cancer tissues and normal mucosa, enrichment of WT (wild type) vs CTLA4_KO (knockout) upregulated gene set and clinical significance were analyzed. The expression of CTLA4,CD3 and granzyme A (GZMA) were validated on 30 cases of Chinese GC. MSI marker MLH1 and EBV marker EBER were examined on 30 cases of Chinese GC by immunohistochemistry and in situ hybridization. Results: CTLA4 was up-regulated in GC tissue relative to normal mucosa in datasets of GSE27342 (fold change=1.586, P<0.001) and GSE63089 (fold change=1.365, P<0.001). Increased CTLA4 expression was positively related to CTLA4 activation. EBV-associated GC (EBVaGC) and microsatellite instability GC (MSIGC) disclosed higher CTLA4 levels than other GCs. Genomic stability GC (GSGC) also showed higher enrichment score of CTLA4 activation. CTLA4 activation resulted in shorter overall survival in GC. The expression level of CTLA4 was well correlated to GZMA (R=0.701, P<0.001) and CD3 (R=0.750, P<0.001). Conclusions: GSGC was firstly identified as the potential GC subtypes responsive to anti-CTLA4 treatment. Note: This abstract was not presented at the meeting. Citation Format: Yingyan Yu. Identification of discrepancy between CTLA4 expression and CTLA4 activation in gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1497.