Abstract 4776: The role of angiogenesis in gastric tumorigenesis

Abstract

Abstract Introduction: Gastric or stomach cancer remains one of the most lethal malignancies, with an estimated 1,089,103 new cases and 768,793 deaths worldwide in 2020. In the United States, it is estimated that there were 26,500 new cases and 11,130 deaths from stomach cancer in 2023. Unfortunately, despite improved treatment in recent years, ~65% of gastric cancer patients present with aggressive metastatic disease, and they die within one year of diagnosis. Therefore, the identification of newer and effective therapies to target the precancerous stages of the disease promises possibilities for the prevention of gastric cancer in patients harboring these lesions. Gastric metaplasia and dysplasia are precancerous lesions that often progress to gastric cancer. Since anti-VEGF-A anti-angiogenic agents have shown efficacy in advanced gastric cancer patients, we hypothesized that VEGF-A-mediated angiogenesis has a functional role in the pathogenesis of gastric metaplasia and dysplasia. Experimental Procedures: The Initial experiments were undertaken in human gastric metaplasia and dysplasia tissues and murine gastric metaplasia and dysplasia tissues collected from a well-established Helicobacter felis (H. felis) induced murine model of gastric tumorigenesis simulating human patients to detect angiogenesis (CD31/MVD) and identify angiogenic pathways using GeoMx DSP Spatial Proteomics and NanoString nCounter assay. Thereafter, further experiments were undertaken in the H. felis-induced murine model of gastric metaplasia and dysplasia, simulating human patients using VEGF-A hypo mice to determine the role of VEGF-A-induced angiogenesis in the progression of these lesions. Results and Conclusion: Although our results indicated angiogenesis and VEGF-A expression in both human and mouse gastric metaplasia and dysplasia, inhibition in the progression of the precancerous gastric lesions was observed in only 40% of the VEGF-A hypo mice, thereby suggesting that VEGF-A induced angiogenesis might not be the major angiogenic pathway in these precancerous lesions in every patient. A similar phenomenon is also seen in some gastric cancer patients. Citation Format: Venu Akkanapally, SUJIT BASU. The role of angiogenesis in gastric tumorigenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4776.