Abstract 4650: The impact of GLI3 mutations and expression on prognosis in gastric cancer

Abstract Background: GLI3, a member of the GLI zinc finger family, has been extensively investigated in various cancers, including gastric cancer. It has been observed that GLI3 is significantly upregulated in solid cancer types. These findings suggest the involvement of GLI3 in the malignant progression of different cancers. However, the precise impact of GLI3 mutations and expression on the prognosis of gastric cancer patients remains unclear. Further investigation is warranted to elucidate the prognostic significance of GLI3 alterations in gastric cancer. Methods: This study included 269 gastric cancer patients from TCGA and 2903 patients from China. The mutation rate of GLI3 was analyzed using Excel. Additionally, the survival rates of gastric cancer patients with GLI3 mutations were compared to those with wild-type using KM survival curves in the TCGA cohort. In addition, the impact of high and low expression of GLI3 on survival was analyzed using a 50% threshold. The expression of GLI3 in tumor tissues were evaluated using Mann-Whitney analysis to compare with those in normal tissues. Results: The mutation rate of GLI3 was 13.55% in the TCGA cohort, whereas it was significantly lower at 7.79% in the Chinese cohort. KM curve analysis demonstrated that patients with GLI3 mutations in the TCGA cohort had a significantly higher survival rate than those with the wild group (p < 0.05). Additionally, GLI3 expression was significantly higher in tumor tissues compared to normal tissues (p < 0.01). Furthermore, based on GLI3 expression analysis, patients with a 30% higher expression of GLI3 had a significantly worse prognosis compared to the remaining 70% of patients (p < 0.05). The analysis of GLI3 mutations and expression revealed that patients with GLI3 mutations had significantly lower RNA expression compared to those with the wild-type. Conclusion: The mutation rate of GLI3 was found to be higher in the TCGA cohort compared to the Chinese cohort. Both GLI3 mutations and expression were closely associated with the prognosis of gastric cancer patients. These findings highlight the significance of GLI3 as a potential prognostic indicator in gastric cancer. Further research is needed to elucidate the underlying mechanisms and validate these observations in larger and more diverse patient populations. Citation Format: Wanfu Zhang, Wendi Jin, Hongwei Wan, Chao Niu, Chu Yan, Chunxiao Wang, Juanjuan Liu, Xiaogang Li, Qinglan Zong, Ning Gao, Ding Zhang. The impact of GLI3 mutations and expression on prognosis in gastric cancer [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 4650.