Abstract 4661: PTPRT mutations in gastric cancer: prognostic implications and functional domain analysis

Abstract Background: The PTPRT gene is recognized as a tumor suppressor in human cancers. However, prior investigations have predominantly concentrated on PTPRT mutations in colon cancer, leaving a dearth of information regarding gastric cancer. Existing studies have proposed that mutations in the PTPRT phosphatase domain are infrequent in common human cancers and have no bearing on prognosis. Conversely, our research on gastric cancer has produced conflicting outcomes, thus presenting an alternative perspective. Methods: This study included a cohort of 369 gastric cancer patients from TCGA database and 234 gastric cancer patients from real-world settings. The mutation rate of the PTPRT gene in gastric cancer patients and the mutations at different functional domain sites were analyzed using EXEL. Furthermore, the impact of mutations in different functional domain sites on survival was assessed using Kaplan-Meier survival curves. Results: The mutation rate of PTPRT was 10.84% (40/369) in the TCGA cohort and 11.54% (27/234) in the real-world cohort. The predominant mutations were observed in the Tyrosine-protein phosphatase domain, accounting for 52.50% (21/40) of total mutations in the TCGA cohort and 37.04% (10/27) in the real-world cohort. Additional mutations were also detected in domains such as Fibronectin type-III and HAM. Survival analysis of the TCGA cohort demonstrated that patients with PTPRT mutations had significantly higher survival rates compared to those with wild-type PTPRT (p=0.0197). Specifically, patients with mutations in the Tyrosine-protein phosphatase domain exhibited significantly improved survival outcomes compared to the remaining patients (p=0.0325). However, there were no significant differences in survival among patients with mutations in other functional domains (p>0.05). Conclusion: In summary, our study elucidated a mutation rate of approximately 10.84% (TCGA cohort) and 11.54% (real-world cohort) for the PTPRT gene in gastric cancer. The Tyrosine-protein phosphatase domain emerged as the primary hotspot for these mutations. Notably, patients harboring PTPRT mutations, particularly in the Tyrosine-protein phosphatase domain, exhibited significantly improved survival outcomes compared to those without mutations in this domain. These findings underscore the potential prognostic significance of PTPRT mutations in gastric cancer and emphasize the need for further investigations to explore their therapeutic implications. Citation Format: Jianbiao Xu, Lei Zou, Yun Shang, Tongmin Wang, Jianlin Song, Wenchuan Zhu, Yunjun Zeng, Jianxun Wang, Chuntao Li, Qinglan Zong, Ning Gao, Ding Zhang. PTPRT mutations in gastric cancer: prognostic implications and functional domain analysis [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 4661.