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Integrated Plasma Proteomic and Tumor Transcriptomic Analysis Identifies Targetable Ligand-Receptor Signaling Axes in Prostate Cancer

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Cytokines and growth factors contribute to prostate cancer (PCa) progression, but the specific ligand-receptor (L-R) interactions linking circulating plasma proteins to tumor signaling require further exploration. To address this, I integrated plasma proteomics with curated L-R networks, tumor transcriptomics, and clinical outcomes. Plasma proteins from PRACTICAL and UK Biobank GWAS data were mapped to L-R interactions using OmniPath Intercell database. These interactions were filtered by expression of receptor genes in Prostate Adenocarcinoma (PRAD) TCGA data, and prioritized through progression free survival analysis. Co-expression analysis was then used to identify L-R pairs with coordinated transcriptional activity. This approach narrowed thousands of initial candidates to a focused set of biologically relevant interactions. Among these, PDGF – PDGFR-⍺, TGF-β – ENG, and FGF – FGFR1 correspond to established tumor promoting pathways.

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