Cellular, chromatin-accessibility, and spatial contextualization of bulk transcriptional patterns linked to positive peritoneal cytology in endometrial cancer.

PPC-positive endometrial cancers are linked to increased stromal/mesenchymal activity and decreased cytotoxic/antigen-presentation transcriptional programs, correlating with poorer outcomes.

• Why it matters: Understanding the transcriptional and cellular origins of PPC can improve prognostic markers and therapeutic strategies for endometrial cancer patients.
• What they did: Analyzing bulk RNA patterns in 408 tumors from TCGA-UCEC, combined with single-cell, chromatin-accessibility, spatial datasets, and qRT-PCR, to identify cellular sources and spatial organization of PPC-associated programs.
• The result: PPC-positive tumors show enrichment of EMT, hypoxia, TGF-beta signaling, and angiogenesis, with reduced cytotoxic lymphocyte activity, and PPC is associated with significantly shorter progression-free, overall, and disease-specific survival; Program B localizes to NK/CD8 compartments, while Program A is stromal-vascular, but tumor CD274 does not modify PPC prognosis.