Abstract 1157: Molecular signatures associated with the progression from DCIS to IDC

Abstract Patients with ductal carcinoma in situ (DCIS) are frequently overtreated. Identifying markers that accurately predict which cases of ductal carcinoma in situ (DCIS) would progress to invasive ductal carcinoma (IDC) is crucial to personalized medicine but remains a challenge. Deciphering the process of DCIS progression at cellular, molecular and genetic levels helps identify biomarkers, allowing for better informed clinical decision-making. To study molecular signatures associated with the progression from DCIS to IDC, we collected samples from breast cancer patients with co-occurring DCIS and IDC, and performed Visium spatial transcriptomics (ST), single-nucleus RNA sequencing and multiplex imaging on these samples. We identified MGP, SLC39A6, PLAT, MLPH, AZGP1, TFF1 and TFF3 as showing significant differential expression levels in DCIS compared to IDC from ST analysis, which was confirmed with snRNA analysis. Notably, in multiplex imaging, MGP and PLAT showed consistently higher expression in DCIS compared to IDC at the protein level. Moreover, we evaluated these molecular signatures using MMTV-PyMT genetic mouse models at various breast cancer progression stages (3, 6, 12, 15, and 20 weeks) with snRNA-seq and multiplex imaging platforms. Collectively, our findings highlight the importance of identifying biomarkers at the molecular level, and provide potential predictive biomarkers for DCIS progression. Citation Format: Siqi Chen, Alla Karpova, Preet Lal, Erik Storrs, Reyka Jayasinghe, Michael Iglesia, Andrew Houston, Yanyan Zhao, Andrew Shinkle, Chia-Kuei Mo, John Herndon, Feng Chen, William Gillanders, Li Ding. Molecular signatures associated with the progression from DCIS to IDC [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 1157.