Abstract PS2-10-05: Association of clinicopathologic features with plasma protein expression in primary invasive breast cancer patients

Abstract Background: Liquid biopsies using blood provide a less invasive method for cancer detection and treatment assessment compared to conventional tissue biopsies. The plasma proteome involves secreted proteins from various organs and tissues, making it a prime candidate for extensive biomarker discovery. However, the vast dynamic range of protein abundance in plasma presents a challenge. In this study, we employed a highly sensitive aptamer-based assay to explore plasma proteins associated with breast cancer (BC). Methods: The subjects were enrolled and specimens were collected through the Clinical Breast Care Project using IRB-approved protocols. We analyzed 260 heparinized plasma samples from breast cancer patients at primary diagnosis, prior to neoadjuvant chemotherapy and excisional surgery. Patients with stage IV, prior DCIS, synchronous breast cancer, or relapse within 6 months were excluded. SomaScan Assay 7k (Somalogic Inc, USA) using 7289 aptamers for human proteins was performed. The association of each clinicopathologic feature of the cohort with plasma protein expression was evaluated using linear regression. The clinical features with notable effect size were further subjected to differential expression analysis using Limma with matched samples followed by pathway analysis using Ingenuity Pathway Analysis (IPA) tool. Results: The protein expression levels were significantly (FDR < 0.05) associated with age, race and stage groups. Differential expression using matched subsets identified 359 significant (FDR < 0.05, |FC| > 1.2) differentially expressed proteins (DEPs) between old (>60 years, n = 44) and young (<40 years, n = 44), and 184 between Caucasian (n = 67) and African American (n = 67) sample groups. We utilized data from Peptide Atlas, and existing literature on normal aging and established cancer biomarkers to contextualize the significant proteins. Pathways significantly (p val < 0.05, |z score| > 2) upregulated in the old group included immune response (cytokine signaling, neutrophil degranulation etc.) and tumor related (PAK, SNARE signaling etc.) pathways. Pathways identified in young were PPAR, DHCR4 signaling, and LXR/RXR activation. For the race group, there were 11 significant pathways upregulated in Caucasians that included FAK and S100 family signaling. For the higher (n = 62) and lower (n = 62) stage comparison, there were 127 significant DEPs (p val < 0.01, |FC| > 1.2) with several cancer-related signaling pathways upregulated in higher stage group (VEGF, SCF-KIT etc.). To explore potential markers of relapse, we conducted a subgroup analysis within the higher-stage cohort, comparing patients who relapsed (n = 30) to those who did not (n = 30) that identified 24 significant DEPs (p < 0.05, |FC| > 1.2) LASSO regression with leave-one-out cross-validation (LOOCV) resulted in a predictive model comprising 18 proteins, achieving a classification accuracy of 0.92. Conclusion: This study identified plasma proteins associated with age group, race and tumor stage in breast cancer patients. These findings indicate that BC related plasma protein expression differs across age and racial groups, a factor to consider in drug target development. We also identified 18 proteins that are potential markers for BC relapse. The identified proteins need to be validated in samples of large cohort. Disclaimer: The contents of this publication are the sole responsibility of the author(s) and do not necessarily reflect the views, opinions, or policies of Uniformed Services University of the Health Sciences (USUHS), the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., the Department of Defense (DoD) or the Departments of the Army, Navy, or Air Force. Mention of trade names, commercial products, or organizations does not imply endorsement by the U.S. government. Citation Format: A. Praveen Kumar, P. Raj-Kumar, J. Liu, B. Deyarmin, B. Mostoller, C. Larson, H. Blackburn, D. Teeter, K. Miller, M. Johnson, M. Russo, L. Fantacone-Campbell, J. Hooke, C. Shriver, H. Hu, A. Kovatich, X. Lin. Association of clinicopathologic features with plasma protein expression in primary invasive breast cancer patients [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-10-05.