ObjectiveTo explore the differentially expressed genes (DEGs) in high-grade serous ovarian cancer (HGSOC)and its clinical significance.MethodsA data set of gene chips GSE54388 related to HGSOC was downloaded from the GEO database, DEGs were screened by using the R language software, and enrichment analyses were performed by using the DAVID database. A total of 35 tissue samples of HGSOC patients were selected, including ovarian cancerous tissues and paracancerous tissues >1 cm away from cancerous tissues, and the real-time fluorescent quantitative PCR was employed to detect DEGs expressions in ovarian cancerous tissues and paracancerous tissues. The STRING database and Cytoscape 3.8.0 software were used to establish protein-protein interaction (PPI) network for screening the core genes. ResultsA total of 537 DEGs were screened in GSE54388 data set, therein, there were 369 down-regulated expressed genes and 168 up-regulated expressed genes. The results of real-time fluorescent quantitative PCR revealed that mRNA expressions of PEX5L, ITLN1, and SLC4A4 in ovarian cancerous tissues were lower than those in paracancerous tissues (P<0.05). The results of enrichment analyses depicted that DEGs were enriched in cellular compositions of extracellular space and extracellular matrix, etc., were involved in molecular functions of heparin binding and calcium ion binding, etc., participated in biological processes in terms of cellular adhesion, division, and proliferation, etc., and were related to Ras signaling pathway, pathway in cancer, etc. A total of 10 core genes were screened from PPI network, namely, CDK1, CDC20, cyclin B1, BUB1B, KIF20A, DLGAP5, NDC80, NCAPG, TTK, and KIF11. ConclusionPEX5L, ITLN1, and SLC4A4 may be the key DEGs for affecting the occurrence and development of HGSOC, and Ras signaling pathway, phosphoinositide 3-kinase signaling pathway, canonical Wnt signaling pathway may be involved in regulating HGSOC progression.