Abstract 776: Identifying gene expression patterns in intraductal carcinoma of the prostate using spatial gene expression analysis: Potential for new biomarkers and treatments

Abstract Introduction and Objective: Intraductal carcinoma of the prostate (IDC-P) is a form of prostate cancer where abnormal cells grow inside the ducts and glands, while the outer basal cell layer stays intact. IDC-P is often linked to certain genetic changes, including TMPRSS2-ERG fusions, as well as mutations or deletions in key genes like TP53, RB1, and PTEN. Given these findings, NCCN guidelines advise early genetic testing for IDC-P patients. Correctly diagnosing IDC-P and applying this knowledge to tailor treatments is essential for improving patient outcomes. Methods: We performed spatial gene expression analysis (using CytAssist Visium) on prostate cancer tissue samples with IDC-P. The goal was to identify gene abnormalities that could help in diagnosing IDC-P or serve as targets for future treatments. We analyzed how gene expression was distributed in IDC-P regions compared to other parts of prostate cancer tissue. Results: Our analysis showed that IDC-P regions had a unique gene expression profile, distinct from other prostate cancer areas. Specific genes such as MUC6, MYO16, NPY, and KLK12 were highly expressed in IDC-P, and these genes are associated with more aggressive cancer behavior. Additionally, genes related to hypoxia like HIF1A, BNIP3L, PDK1, and POGLUT1 were highly upregulated in IDC-P areas. At the same time, markers for immune cells (CCR5, FCGR3A) and fibroblasts (CCL5, TRAC) were downregulated. This suggests that IDC-P may be more aggressive due to hypoxia and fewer immune and fibroblast cells in the tumor environment. Conclusions: This study used spatial gene expression analysis to characterize IDC-P (Watanabe et al., IJMS 2024), providing valuable insights. However, this method also has some challenges, such as capturing signals from different cell types in the same spots, which makes it harder to distinguish between them. In future studies, combining spatial gene analysis with single-cell RNA sequencing or using more advanced techniques like Xenium could address these challenges. We are currently working on those studies and will be able to present the latest data on the day of the presentation. These approaches may help identify new diagnostic markers and lead to more personalized treatment options for patients with IDC-P. Citation Format: Ryuta Watanabe, Haruna Arai, Mie Kurata, Noriyoshi Miura, Riko Kitazawa, Tadahiko Kikugawa, Takashi Saika. Identifying gene expression patterns in intraductal carcinoma of the prostate using spatial gene expression analysis: Potential for new biomarkers and treatments [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 776.