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


ABSTRACT: PurposeHigh-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.MethodsWe 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.ResultsAll 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.ConclusionTaken together, the findings of this study may provide novel insights into HGSOC chemoresistance and identify important therapeutic targets.

SUBMITTER: Wu Y 

PROVIDER: S-EPMC7335306 | BioStudies | 2020-01-01

SECONDARY ACCESSION(S): 10.18632/oncotarget.19048

REPOSITORIES: biostudies

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Publications

The molecular mechanisms of chemoresistance in cancers.

Zheng Hua-Chuan HC  

Oncotarget 20170706 35


Overcoming intrinsic and acquired drug resistance is a major challenge in treating cancer patients because chemoresistance causes recurrence, cancer dissemination and death. This review summarizes numerous molecular aspects of multi-resistance, including transporter pumps, oncogenes (EGFR, PI3K/Akt, Erk and NF-κB), tumor suppressor gene (p53), mitochondrial alteration, DNA repair, autophagy, epithelial-mesenchymal transition (EMT), cancer stemness, and exosome. The chemoresistance-related protei  ...[more]

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