ObjectiveTo investigate epithelial cell heterogeneity in ovarian cancer (OC) and its impact on the tumor microenvironment (TME) by constructing OC epithelial subtypes using publicly available single-cell RNA sequencing (scRNA-seq) data and bioinformatics approaches.MethodsEight cell types and gene expression matrices were identified from the GSE118828 OC scRNA-seq dataset, and a deconvolution approach was used to estimate cellular composition in bulk RNA sequencing (bulk RNA-seq) data. OC samples were stratified into high-epithelial (C1) and low-epithelial (C2) subtypes based on epithelial cell abundance. Differences in overall survival (OS) and immune microenvironment features between patients with C1 and C2 subtypes were analyzed. Differentially expressed genes (DEGs) between C1 and C2 subtypes, as well as between early-stage (stage Ⅰ~Ⅱ) and late-stage (stage Ⅲ-Ⅳ) OC groups were identified to screen epithelial-related genes associated with OC progression, and their influence on the TME was analyzed. Protein expression of the epithelial-related genes in OC progression was validated using data from the Human Protein Atlas (HPA) database.ResultsPatients with the C1 subtype exhibited significantly better OS compared to those with C2 subtype(P < 0.05). The C1 and C2 subtypes demonstrated distinct immune microenvironment infiltration profiles. Infiltration levels of T helper(Th) cells, M1 macrophages, and activated dendritic cells (DCs) were significantly higher in the C1 subtype (all P < 0.05). In late-stage OC patients with C1 subtype, the expression of HAS1, DAPL1, and ADH1B was significantly upregulated (all P < 0.05). Furthermore, DAPL1 expression was positively correlated with the degree of macrophage and regulatory T cells (Treg) infiltration in OC (P < 0.05). HPA database analysis confirmed that DAPL1 protein expression was significantly upregulated in OC tissues.ConclusionThe high-epithelial subtype of ovarian cancer may exert anti-tumor effects through extensive infiltration of T helper (Th) cells, M1 macrophages, and activated dendritic cells within the tumor microenvironment. Conversely, upregulation of the epithelial-related gene DAPL1 may induce the infiltration of macrophages and Treg, thereby promoting OC progression.