Abstract LB259: Development of a CTC based assay to characterize MAOA expression in metastatic prostate cancer

Abstract

Background: Monoamine oxidase A (MAOA) is best known for its role in neurotransmitter regulation and as the target for MAO inhibitors used as first-generation antidepressants. MAOA expression is associated with poor outcomes and treatment resistance in many cancers. In prostate cancer, MAOA over-expression is associated with high histologic Gleason grade and resistance to androgen-targeting and cytotoxic agents. MAO inhibitors have demonstrated anti-cancer activity in many laboratory studies and in a clinical trial with non-metastatic prostate cancer patients (NCT02217709). Here, we developed and explored the potential clinical utility of a novel assay quantifying MAOA expression in circulating tumor cells (CTCs) from metastatic prostate cancer patients utilizing the RareCyte platform. Methods: Nucleated cells were prepared from whole blood samples collected at various timepoints using the AccuCyte system. The CyteFinder automated immunofluorescent imaging system was used to identify CTCs (CK+/EpCAM+, CD45-) stained with a custom MAOA Rareplex staining assay on a Leica BOND RXm automated ICC stainer. Single-cell MAOA protein level expression, measured as mean fluorescent intensity (MFI), was evaluated in all CTC+ samples. MFI threshold for MAOA+ cells was established to maximize detection accuracy using spike-in controls of MAOA positive (LNCaP) versus MAOA negative (PC3) cells. Clinical data was passively collected from the medical record. Subjects were classified as either castrate-sensitive or castrate-resistant prostate cancer (CSPC or CRPC) based on standard clinical criteria. All data analysis was performed using relevant libraries in R. Results: 79 samples were collected at various treatment timepoints from 46 subjects (CSPC=25, CRPC = 21) with metastatic prostate cancer: age (mean ± SD) 73.5 ±-8.8 years; PSA 30.3 ± 116 ng/dl; metastatic to bone 83% (n=38), lymph nodes 28% (n=13); and other visceral sites 22% (n=10). MAOA+ CTCs were observed in 45% (n=18/40) of CRPC samples versus 10% (n=4/39) of CSPC samples (p<0.05, Fisher’s exact test). Cox proportional hazard analysis revealed that the presence of MAOA+ CTCs in CRPC patients at baseline was associated with poor overall survival (HR: 4.50, 95%CI: 1.25-16.2; p<0.05). Conclusions: A CTC-based assay was developed and used to explore MAOA expression in a pilot cohort of patients with metastatic prostate cancer. We observed significantly increased MAOA expression in CRPC versus CSPC and worse overall survival in MAOA+CTC+ CRPC patients. These data suggest potential clinical utility for a CTC-based MAOA assay, which merits additional validation in expanded patient cohorts. Citation Format: Daniel Bsteh, Caelin Brenninkmeijer, Hyun O. Choi, Seok Hee Jang, Chun-Peng Liao, David B. Agus, Amir Goldkorn, Mitchell E. Gross. Development of a CTC based assay to characterize MAOA expression in metastatic prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited s); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2): nr LB259.