Spatial proteo-transcriptomic profiling reveals the molecular landscape of borderline ovarian tumors and their invasive progression

Epithelial serous borderline tumors (SBT) are non-invasive neoplastic ovarian lesions that may recur as chemo-resistant low-grade serous cancer (LGSC). While genetic alterations suggest a common origin, the transition from SBT to LGSC remains poorly understood. Here, we integrate cell-type resolved spatial proteomics and transcriptomics to elucidate the evolution from SBT to LGSC and its corresponding metastasis in both the stroma and the tumor. We show that the transition of SBT to LGSC occurs in the epithelial compartment through an intermediary stage with micropapillary features. LGSC overexpressed the c-Met receptor tyrosine kinase and several CNS-specific proteins. In the tumor microenvironment, interconnectivity between cancer and tumor cells and enzymes degrading a packed extracellular matrix suggests functional collaboration between various cells in the tumor organ. Integrating spatial transcriptomics and proteomics, we functionally validate 16 drug targets. ROIs of a total of four cohort groups were studied in the epithelial and stromal compartment on ovarian cancer: serous borderline tumors (SBT), micropapillary SBT (SBT-MP), low-grade serous cancer primary tumors (LGSC-PT) and corresponding metastases (LGSC-Met).