Abstract 2655: Abundance of intra-tumoral angiogenesis is associated with attenuated tumor aggressive biology, tumor microenvironment, as well as worse survival in gastric cancer patients

Abstract

Abstract Background: Across the world, gastric cancer is the third leading cause of cancer deaths. There is an urgent need to develop a predictive biomarker that help guide treatment decision-making to precisely address gastric cancer progression and metastasis. Angiogenesis is the creation of de novo blood vessels from existing ones, and it is a cornerstone of cancer as it paves the way for cancer progression and metastasis. Angiogenic factors such as vascular endothelial growth factor (VEGF) and endothelial cell growth factor (EGF) are produced by cancer and stromal cells in many types of cancers including gastric cancer. We hypothesized that intra-tumoral angiogenesis plays a role in gastric cancer aggressiveness. Methods: The angiogenesis level of tumors from 1,348 gastric cancer patients in multiple cohorts was measured using the Gene Set Variation Analysis (GSVA) method to score tumor transcriptomes with the Hallmark angiogenesis gene set. Results: Gastric cancers with high angiogenesis score were significantly associated with high expression of multiple angiogenesis-related genes including VEGF-related, endothelial cell marker-related, and vascular stability-related genes in the TCGA and GSE84437 cohorts. Furthermore, in both cohorts, the angiogenesis score was moderately correlated with not only vessel-related stromal cells (endothelial cells [spearman r = 0.557, 0.473], lymphatic [r = 0.520, 0.597] and microvascular endothelial cells [r = 0.470, 0.460], and pericytes [r = 0.555, 0.301]), but also fibroblasts (r = 0.485, 0.467) and chondrocytes (r = 0.565, 0.601) in the tumor microenvironment. Tumors with high angiogenesis score were associated with a lower fraction of Th1, Th2, and dendritic cells, and a higher fraction of M1 macrophages compared with low angiogenesis score tumors. Gastric cancer with a high angiogenesis score was enriched with coagulation, epithelial mesenchymal transition, hypoxia, and TGF-β signaling gene sets in the TCGA, GSE84437, and GSE26253 cohorts. Interestingly, a high angiogenesis score was significantly associated with greater AJCC stage and T-category, but not N-category. Finally, patients with a high score had significantly shorter survival in three cohorts (overall survival: p = 0.002 in the TCGA, p < 0.001 in the GSE84437, and disease-free survival: p = 0.011 in GSE26253). Conclusion: The angiogenesis score can be a useful tool to assess intra-tumoral angiogenesis, which is associated with clinical outcomes in gastric cancer patients. Citation Format: Masanori Oshi, Tae Hee Kim, Vikas Satyananda, Fernando A. Angarita, Yoshihisa Tokumaru, Li Yan, Ryusei Matsuyama, Itaru Endo, Kazuaki Takabe. Abundance of intra-tumoral angiogenesis is associated with attenuated tumor aggressive biology, tumor microenvironment, as well as worse survival in gastric cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2655.