Abstract LB257: Development of a whole blood RNA assay to explore expression of MAOA and KLK3 with clinical outcomes in metastatic prostate cancer patients

Abstract Background: Prostate cancer remains a leading cause of morbidity and mortality in men, necessitating refined management strategies. Prostate-specific antigen (PSA) is commonly used as a marker of therapeutic efficacy in metastatic prostate cancer. However, serum PSA levels may not be elevated or accurately reflect therapeutic response in some patients, especially those with neuroendocrine or aggressive disease variants. Kallikrein 3 (KLK3) codes for PSA and has been used as a component of whole blood based prognostic assays. Monoamine oxidase A (MAOA) has been associated with treatment resistance and neuroendocrine prostate cancer cells and tissue in vitro. We developed a whole-blood RNA expression-based assay to explore relationships between MAOA and KLK3 expression with clinical variables and outcomes in metastatic prostate cancer patients. Methods: A standardized workflow was developed using the PaxGene RNA tube system to establish sensitive detection of MAOA and KLK3 based on LNCaP human prostate cancer cells spiked into control human blood. Relative expression levels across samples were compared using the 2-ΔCT method. Whole-blood RNA samples were collected from patients with metastatic prostate cancer under an IRB-approved protocol. Clinical information was obtained from the medical record. Cutoff values for MAOA and KLK3 expression levels were calculated based on maximally selected rank statistics for survival analysis using the conditional Monte Carlo method with the maxstat library in R. Results: This pilot sample set included analysis of 130 samples collected at various timepoints from 49 patients. Age (mean ± SD) 72.4 ±-9.5 years; serum PSA 43.7±147 ng/dl; Bone metastasis (n= 28/49) 82%. MAOA expression was found to be highly variable across samples and was not associated with serum PSA or KLK3 expression levels. Serum PSA was weakly correlated with KLK3 expression (Spearman’s Rho = -0.259, p<0.05). Elevated MAOA and KLK3 expression were associated with worse overall survival in patients with castrate-resistant prostate cancer. Longitudinal analysis identified examples of increasing MAOA expression associated with resistance to taxane chemotherapy and metastatic progression without concomitant increases in KLK3 expression or increased serum PSA. Conclusions: We developed blood-based assay for relative quantitation of MAOA and KLK3 expression from whole-blood in metastatic prostate cancer patients. Our data confirms that KLK3 expression is associated with poor clinical outcomes and suggests that increased MAOA expression can be associated with chemotherapy-resistant prostate cancer. Serial assessment of MAOA levels may add to standard assessment of serum PSA to help guide treatment decisions in caring for advanced prostate cancer patients. Citation Format: Caelin Brenninkmeijer, Hyun O. Choi, Seok Hee Jang, Miles King, Chun Peng Liao, Mary Duong, David B. Agus, Mitchell E. Gross. Development of a whole blood RNA assay to explore expression of MAOA and KLK3 with clinical outcomes in metastatic prostate cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr LB257.