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Abstract
Background: Emerging evidence suggests that there is a complex interplay between ethnicity and disease biology in metastatic hormone sensitive prostate cancer (mHSPC). We examined digital spatial profiling with GeoMx to evaluate differential protein expression between non-Hispanic/non-Latino (NHL) and Hispanic/Latino (HL) patients with mHSPC. Methods: Pre-treatment prostate biopsy specimens were obtained from patients on a clinical trial as part of an IRB approved protocol. The GeoMx Digital Spatial Profiler (DSP) was used to evaluate protein expression in selected regions of interest (ROIs). Differential expression analysis was performed using R (v 4.4.2). To determine significant differences in protein expression, a false discovery rate (FDR)-adjusted q-value was applied and a Log2Fold change (Log2FC) with a q-value < 0.01 was considered significantly differentially expressed. Results: A total of 8 patients (4 NHL and 4 HL) were enrolled at City of Hope including network sites and who had pre-treatment biopsy specimens that were available for digital spatial profiling analysis. We examined the Log2FC between protein expression in NHL and HL patients and filtered for q-values < 0.01. We identified multiple proteins that were significantly differentially expressed. Proteins that were more highly expressed (Log2FC > 1) in NHL patients included CD44, fibronection, and Ki-67. Proteins that were more moderately expressed (Log2FC < 1) in NHL patients included beta-2 microglobulin and. In contrast, HL patients were found to have higher expression in BCL6, CD68, CD80, Foxp3, PARP, and STING (Log2FC < 0). Conclusions: Digital spatial profiling with GeoMx reveals significant differences in protein expression in NHL vs. HL patients with mHSPC. Notably, these include markers of cancer stem cells (CD44), DNA damage pathway proteins (PARP), and both immunoregulatory (Foxp3) and immunostimulatory (STING) proteins. This may have both prognostic and therapeutic implications. Citation Format: Peter D. Zang, Joe Bonner, Alexander Chehrazi-Raffle, Lixin Yang, Natasha Garg, Swapnil Rajurkar, James Shen, Naveen Gupta, Amartej Merla, Sumanta Pal, Raju Pillai, Stephen Gruber, Tanya B. Dorff. Digital spatial profling with GeoMx to identify differential protein expression in Non-Hispanic/Latino and Hispanic/Latino Patients with metastatic hormone sensitive prostate cancer [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 5103.
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