Abstract 5918: Vascular endothelial growth factor A (<i>VEGF-A</i>) gene expression profiling in Northern Thai gastric cancer patients and potential biomarker for anti-VEGF therapy selection

Abstract Background: Vascular endothelial growth factor (Anti-VEGF) drugs are used to treat advanced-stage gastric cancer to inhibit angiogenesis, which is the process of new blood vessel formation that tumors need to grow. These drugs have improved progression-free survival and overall survival when combined with traditional chemotherapy as the second-line treatment. However, the effectiveness of these drugs can vary among patients. Some patients may have tumors that do not express high levels of VEGF-A, making the drugs less effective. Additionally, the high cost of these treatments can be a barrier for many patients. This study aims to profile VEGF-A gene expression in the Thai population and investigate the relationship between VEGF-A and IL-8, a poor prognostic marker for advanced-stage gastric cancer, before and after chemotherapy. Methods: From 2006 to 2018, 149 patients with advanced-stage gastric cancer were collected from Maharaj Nakorn Chiang Mai Hospital in Thailand. These gastric mucosal biopsy tissues were investigated for IL-8 and VEGF-A gene expression using the RT-qPCR technique with specific primer probes for particular genes. Results: In pre-chemotherapy conditions, 71.15% of 52 cancer gastric mucosal biopsy tissues had higher levels of IL-8 gene expression than the adjacent normal tissue. In contrast, only 31.51% of 73 cancer tissues had higher levels of VEGF-A gene expression than adjacent normal tissue, low expression in 10, 13.7% of patients, and 40, 54.79% of patients showed down-regulate or no expression of VEGF-A in cancer tissue in tumor and adjacent normal tissue in the pre-chemotherapy group. Furthermore, when investigating both IL-8 and VEGF-A expression in the same tissues under pre-chemotherapy conditions, the results indicated that most samples had an independent correlation between IL-8 and VEGF-A levels. Specifically, 27.66% of 47 cancer tissues exhibited higher IL-8 but lower VEGF-A levels than adjacent normal tissues in the same patient controls. However, in the subgroup analysis, three of six, 50% of patients with post-chemotherapy conditions showed downregulation of the IL-8 gene. While only two of nine, 22.22% of patients demonstrated downregulation from post-chemotherapy, and one of nine, 11.11% of patients demonstrated up-regulation post-chemotherapy. There were 6 out of 9, 66.67% patients had no up or down-regulation. Therefore, VEGF-A could be used as a specific biomarker for targeted therapy for advanced gastric cancer, as its expression level did not correlate with IL-8 levels or prior chemotherapy treatment. Conclusion: The authors found that 23 out of 73, 31.51% of patients had VEGF-A expression in pre-chemotherapy conditions. The authors recommend that VEGF-A gene expression levels should be tested in patients who intend to use anti-VEGF drugs. Citation Format: Amonnat Sukhamwang, Hathairat Thananchai, Supachai Yodkeeree, Pornngarm Dejkriengkraikul, Sirikan Limpakan (Yamada). Vascular endothelial growth factor A (VEGF-A) gene expression profiling in Northern Thai gastric cancer patients and potential biomarker for anti-VEGF therapy selection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5918.