Single-cell landscape of autophagy in the metastatic ovarian tumor microenvironment: A cell-type-specific perspective

Autophagy plays a context-dependent role in ovarian cancer progression, functioning as both a homeostatic regulator and a mediator of metastatic adaptation. To characterize the cellular heterogeneity of autophagy within metastatic ovarian carcinoma, a single-cell RNA sequencing (scRNA-seq) analysis was performed using a primary dataset (GSE147082) comprising untreated metastatic tumor samples, followed by validation in an independent ascites-derived cohort (GSE146026). After quality control, clustering, and cell-type annotation, diverse epithelial, immune, stromal, and endothelial populations were identified. Autophagy-related genes curated from Gene Ontology Biological Process (GO:BP) terms demonstrated marked cell-type-specific transcriptional variability. Module scoring using Seurat revealed significant differences in autophagy activity across cell populations in the validation cohort (Kruskal-Wallis p < 2.2 × 10 -16 ), with stromal and myeloid compartments exhibiting distinct enrichment patterns. Differential expression and GO enrichment analyses indicated that stromal cells were associated with extracellular matrix organization and stress-adaptive processes; myeloid cells with immune and lysosomal pathways, and epithelial populations with mitochondrial and metabolic remodelling. Cell-cell communication analysis using CellChat predicted fibroblasts and macrophages as major signalling hubs within the metastatic tumor microenvironment. Together, these findings indicated that autophagy is heterogeneously regulated across metastatic niches and may contribute to tumor-stroma-immune interactions in a cell-type-specific manner. This study provides a single-cell-resolved framework for understanding autophagy within ovarian cancer metastasis.