INTEGRATED BIOINFORMATICS ANALYSIS AND DEVELOPMENT OF A MULTI-BIOMARKER WEIGHTED CLINICAL DECISION SCORE FOR BREAST CANCER RISK STRATIFICATION USING ANGIOGENIC AND INFLAMMATORY SIGNATURES

Abstract

Background: Breast cancer is characterized by complex interactions between angiogenesis, inflammation, and extracellular matrix remodeling. Single biomarkers lack sufficient diagnostic accuracy, necessitating multi marker approaches. Methods: Blood samples from breast cancer patients and healthy controls were analyzed at the Institute of Personalized Oncology, Sechenov University. Circulating inflammatory and angiogenic biomarkers were quantified using the Luminex MAGPIX multiplex platform. 5 biomarkers—Osteopontin, sVEGFR2, sNeuropilin 1, suPAR and Tenascin-C were selected to develop a weighted Clinical Decision Score. Protein–protein interaction analysis of Breast Invasive Carcinoma data from cBioPortal was performed to investigate the molecular interactions underlying the various genes of the selected biomarkers. Results: The weighted Clinical Decision Score (wCDS) demonstrated enhanced biological interpretability by integrating complementary pathways associated with tumor angiogenesis, inflammation, and extracellular matrix remodeling. Increasing scores reflected progressive activation of multiple oncogenic processes and improved biological discrimination compared with equal-weight scoring approaches. Our network analysis identified THBS1–SPP1–PLAU signal axis as a novel pathway in breast cancer pathology, alongside TGFB1 as the principal regulatory hub, while SPP1 (osteopontin gene) emerged as a central connector linking angiogenesis, inflammation, ECM remodeling, and invasion through a TGFB1–SPP1–PLAU signaling axis. Conclusion: This study supports the potential clinical utility of the wCDS as a blood-based risk stratification tool for breast cancer. It also highlights the need for further investigation of the TGFB1–SPP1–PLAU signaling axis as a promising therapeutic pathway and the evaluation of SPP1 as a potential drug target. Furthermore, it advocates for the development of SPP1-targeted therapies for breast cancer by the pharmaceutical industry.