A Prognostic Model Approach to Integrated Transcriptomic and Immune Profiles in Organoids Derived from Breast Cancer Patients
Breast cancer remains a leading global health burden, with rising incidence and mortality despite advances in molecular characterization and targeted therapies. Personalized investigations of tumor biology and medication response are made possible by patient-derived organoids (PDOs), which have emerged as physiologically realistic models that preserve the histological and molecular characteristics of the original malignancies. In order to find subtype-specific transcriptional and immune-related markers, we conducted transcriptome profiling of breast cancer PDOs that represent several molecular subtypes and compared them to non-tumoral breast organoids. NTRK3, SLITRK3, IL1RAP, and IRF2BP2 were consistently upregulated in breast cancer PDOs, indicating the activation of inflammatory and neurotrophin signaling pathways. These modifications were accompanied by increased production and release of pro-inflammatory cytokines IL-1 and IFN-Y, suggesting the presence of an active immune-modulatory phenotype. IL1RAP and IRF2BP2 emerged as potential regulatory centers within the inflammatory signaling pathway, which may affect immune evasion and resistance to treatment. Their consistent upregulation across different subtypes underscores their promise as innovative diagnostic and prognostic indicators, notably in more aggressive forms of breast cancer. Our research emphasizes the importance of combining immune and transcriptomic analyses in PDOs to explore tumor-immune dynamics tailored to individual patients. The discovery of inflammation-related targets such as IL1RAP and NTRK3/SLITRK3 co-partners bolsters their potential utility as markers for disease advancement or as targets for therapy, particularly in high-risk subtypes. These findings emphasize the practical applications of patient-derived organoids as tools for precision oncology and translational studies.