Identification of Chemoresistance-Associated Key Genes and Pathways in High-Grade Serous Ovarian Cancer by Bioinformatics Analyses

• Main Authors: Wu Y, Xia L, Guo Q, Zhu J, Deng Y, Wu X
• Format: Article
• Language: English
• Published: Dove Medical Press 2020-06-01
• Series: Cancer Management and Research
• Subjects: high-grade serous ovarian cancer; chemoresistance; gene expression profiling; bioinformatics analysis.
• Online Access: https://www.dovepress.com/identification-of-chemoresistance-associated-key-genes-and-pathways-in-peer-reviewed-article-CMAR

Yong Wu,1,2,* Lingfang Xia,1,2,* Qinhao Guo,1,2,* Jun Zhu,1,2 Yu Deng,2,3 Xiaohua Wu1,2 1Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 3Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaohua WuDepartment of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai 200000, People’s Republic of China, Tel/Fax [phone]Email [e-mail]: High-grade serous ovarian cancer (HGSOC) is the leading cause of death among gynecological malignancies. This is mainly attributed to its high rates of chemoresistance. To date, few studies have investigated the molecular mechanisms underlying this resistance to treatment in ovarian cancer patients. In this study, we aimed to explore these molecular mechanisms using bioinformatics analysis.Methods: We analyzed microarray data set GSE51373, which included 16 platinum-sensitive HGSOC samples and 12 platinum-resistant control samples. Differentially expressed genes (DEGs) were identified using RStudio. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using DAVID, and a DEG-associated protein–protein interaction (PPI) network was constructed using STRING. Hub genes in the PPI network were identified, and the prognostic value of the top ten hub genes was evaluated. MGP, one of the hub genes, was verified by immunohistochemistry.Results: All samples were confirmed to be of high quality. A total of 109 DEGs were identified, and the top ten enriched GO terms and four KEGG pathways were obtained. Specifically, the PI3K-AKT signaling pathway and the Rap1 signaling pathway were identified as having significant roles in chemoresistance in HGSOC. Furthermore, based on the PPI network, KIT, FOXM1, FGF2, HIST1H4D, ZFPM2, IFIT2, CCNO, MGP, RHOBTB3, and CDC7 were identified as hub genes. Five of these hub genes could predict the prognosis of HGSOC patients. Positive immunostaining signals for MGP were observed in the chemoresistant samples.Conclusion: Taken together, the findings of this study may provide novel insights into HGSOC chemoresistance and identify important therapeutic targets.Keywords: high-grade serous ovarian cancer, chemoresistance, gene expression profiling, bioinformatics analysis