Abstract 5133: Gastric cancer carrying FAT4 mutations associated with favorable prognosis in comparison to wild-type: Results from Real-World Cohorts

Abstract Introduction: Gastric cancer (GC) is a complex and heterogeneous disease with variable clinical outcomes. Identifying prognostic factors that can reliably predict patient outcomes is crucial for personalized treatment strategies. In this study, we aimed to investigate the impact of mutations in the FAT4 gene as potential prognostic factors in gastric cancer. Methods: We conducted a comprehensive analysis of genomic data from a cohort of 236 gastric cancer patients to identify mutations in the FAT4 gene and validated it using the TCGA cohort. The mutational landscape of FAT4 was analyzed using next-generation sequencing (NGS) techniques. Clinical data, including patient demographics, tumor characteristics, and survival outcomes, were collected and correlated with the presence of FAT4 cadherin mutations. Results: In the real-world cohort, the occurrence of mutations of FAT4 was 19.1% (45/236), while in the TCGA cohort, it was 21.0% (89/423). Specifically, the mutation rates in the single cadherin functional domain of FAT4 were 10.2% (24/236) in the real-world cohort and 8.0% (34/423) in the TCGA cohort. The mutation rates for multiple cadherin sites were 2.5% (6/236) and 2.1% (9/423) in the real-world and TCGA cohorts, respectively. Survival analysis revealed that patients with FAT4 mutations had a significantly better prognosis compared to those with wild-type FAT4 (p=0.0357). Patients with multiple cadherin mutations had a better prognosis compared to those with single cadherin mutations in real-world cohorts (p=0.0651). No significant difference was observed in the TCGA cohort between single and multiple cadherin mutations (p = 0.2003), although FAT4 mutations exhibited a significant improvement in prognosis compared to wild-type patients in the TCGA cohort (p = 0.0226). Conclusion: Our findings indicate that FAT4 mutations confer a favorable prognosis in gastric cancer patients. The presence of FAT4 mutations was associated with improved survival compared to patients with wild-type FAT4. These findings underscore the potential value of FAT4 mutation status as a prognostic factor, guiding personalized treatment approaches for individuals with gastric cancer. Citation Format: Shu Wang, Haoyuan Wang, Yuxuan Ma, Yuhao Wang, Yan Zhao, Chaosheng Peng, Weiming Duan, Feilong Zhao, Jianjun Yang. Gastric cancer carrying FAT4 mutations associated with favorable prognosis in comparison to wild-type: Results from Real-World Cohorts [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 5133.