Proteotranscriptomics Reveal Signaling Networks in the Ovarian Cancer Microenvironment

摘要: Ovarian cancer is characterized by early transcoelomic metastatic spread via the peritoneal fluid, where tumor cell spheroids (TU), tumor-associated T cells (TAT), and macrophages (TAM) create a unique microenvironment promoting progression, chemoresistance, immunosuppression. However, underlying signaling mechanisms remain largely obscure. To chart these networks, we performed comprehensive proteomic transcriptomic analyses of TU, TAT, TAM from ascites ovarian patients. We identify multiple intercellular pathways driven protein or lipid mediators that are associated with clinical outcome. Beyond cytokines, chemokines growth factors, include proteins extracellular matrix, immune checkpoint regulators, complement prominent network axon guidance molecules ephrin, semaphorin, slit families. Intriguingly, both TU patients predicted short survival selectively produce supporting prometastatic events, including matrix remodeling, stemness, invasion, angiogenesis, immunosuppression, whereas longer express cytokines linked to effector T-cell chemoattraction activation. In summary, our study uncovers previously unrecognized networks in potential relevance.