Abstract 5969: Intra-tumoral coagulation is significantly associated with EMT, angiogenesis, and worse patient survival in gastric cancer

Abstract

Abstract Background: Bleeding is one of the most commonly observed clinical signs of gastrointestinal cancer. Coagulation regulates inflammation and angiogenesis in cancer, and is associated with tumor development and metastasis. To date, there has been no measures to quantify the state of intra-tumoral coagulation. We hypothesized that intra-tumoral coagulation as quantified using coagulation score is associated with angiogenesis and worse prognosis in gastric cancer. Methods: The coagulation score was determined by the Gene set variation analysis (GSVA) algorithm as GSVA score of the “HALLMARK_COAGULATION” in the MSigDB hallmark gene sets collection. Transcriptome data of 807 gastric cancer patients of TCGA_STAD and GSE84437 cohorts were used for the analysis. Results: We found that high coagulation score was significantly associated with high AJCC T-category (p = 0.018), lymph node metastasis status (p = 0.036), AJCC stage (p = 0.006) in the TCGA cohort. The association of the score with staging were validated by GSE84437 cohort. Further, patients with high score were associated with worse disease-specific survival and overall survival (OS) (p = 0.019 and 0.011, respectively) in the TCGA cohort, and OS in GSE84437 cohort (p = 0.012). Although the coagulation score was not associated with cell proliferation-related nor immune-related signaling, gastric cancer with high coagulation score highly enriched epithelial mesenchymal transition (EMT), myogenesis, apical junction, transforming growth factor (TGF)-β signaling, and angiogenesis consistently in both cohorts (all false discovery rate<0.25). The coagulation score strongly correlated with angiogenesis score, and high coagulation was significantly associated with high infiltration of angiogenesis-related vascular cells, including endothelial cells, microvascular endothelial cells, lymphatic endothelial cells, and pericytes, calculated by xCell algorithm, as well as high expression of angiogenesis-related genes, including Endothelial cell marker, and vascular stability related genes. Conclusion: Intra-tumoral coagulation assessed by coagulation score is associated with clinical outcomes of gastric cancer patients. Citation Format: Masanori Oshi, Joy Sarkar, Rongrong Wu, Li Yan, Ryusei Matsuyama, Itaru Endo, Kazuaki Takabe. Intra-tumoral coagulation is significantly associated with EMT, angiogenesis, and worse patient survival in gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5969.