Single-cell transcriptomics of chicken ovarian cancer identifying immune subsets with prognostic implications

Ovarian cancer (OC) is a lethal gynecological malignancy with a low 5-year survival rate. The lack of preclinical models accurately capturing OC's early pathogenesis contributes to this poor prognosis. The domestic laying hen uniquely develops spontaneous OC, but its single-cell-level insights for pathogenesis have been lacking. Here, we present the first single-cell transcriptomic atlas of ovarian tissues from 110-week-old laying hens with or without OC. We annotated 12 core cellular lineages and characterized tumor-associated changes, including increased CD4+ and CD8+ T cells and reduced macrophages in OC samples. T cells sub-clustering revealed conserved cell subtype-specific pH homeostasis regulation profiles across species. Notably, gene signatures from the two dominant Cyto_CD8+ subsets exhibited opposing prognostic roles when validated against human OC datasets (GSE18520, GSE26712, GSE49997). This study confirms the laying hen as a valuable OC model by demonstrating cross-species conservation in cellular heterogeneity and oncogenic pathways, advancing it from a pathologically analogous system to a molecularly traceable tool.