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Exploration of the sequential gene changes in epithelial ovarian cancer induced by carboplatin via microarray analysis.

ABSTRACT: The purpose of the current study was to explore the carboplatin?induced sequential changes in gene expression and screen out key genes, which were associated with effects of carboplatin on epithelial ovarian cancer (EOC). The microarray dataset GSE13525 was downloaded from the Gene Expression Omnibus database, including 6 EOC cell samples separately treated with carboplatin at 24, 30 and 36 h (case group), and 6 samples treated with phosphate?buffered saline at the same time points (control group). A total of 3 sets of differentially expressed genes (DEGs) were respectively identified in case samples at 24, 30 and 36 h compared with the control group via the Limma package, and separately recorded as DEG?24, DEG?30 and DEG?36. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the overlapped DEGs were performed via the Database for Annotation, Visualization and Integrated Discovery. The protein?protein interaction (PPI) network was constructed and analyzed by Cytoscape software. In addition, the survival curves were drawn to illustrate the association between the expression levels of certain critical genes and the prognosis of EOC. A total of 170, 605 and 1043 DEGs were separately obtained in DEG?24 DEG?30 and DEG?36, and 110 overlaps were identified. The overlaps were enriched in 77 GO terms and 3 KEGG pathways. A total of 152 pairs were involved in the PPI network, and the abnormal expression levels (high or low) of c?Jun and cyclin B1 (CCNB1) would reduce the survival time of patients with EOC. The study indicated that c?Jun and CCNB1 may be the prognostic biomarkers of EOC treated with carboplatin, and certain pathways (such as p53 signaling pathway, cell cycle and mitogen?activation protein kinase signaling pathway) may be involved in carbo-platin?resistant EOC.

SUBMITTER: Wei S

PROVIDER: S-EPMC5547949 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Exploration of the sequential gene changes in epithelial ovarian cancer induced by carboplatin via microarray analysis.

Wei Shuqing S Liu Jianwu J Shi Yuxia Y Zhang Xi X Yang Yongming Y Song Qingzhen Q

Molecular medicine reports 20170715 3

The purpose of the current study was to explore the carboplatin‑induced sequential changes in gene expression and screen out key genes, which were associated with effects of carboplatin on epithelial ovarian cancer (EOC). The microarray dataset GSE13525 was downloaded from the Gene Expression Omnibus database, including 6 EOC cell samples separately treated with carboplatin at 24, 30 and 36 h (case group), and 6 samples treated with phosphate‑buffered saline at the same time points (control grou ...[more]

PMID: 28713952

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Project description:Patients diagnosed with epithelial ovarian cancers (EOCs) often suffer from disease relapse associated with the emergence of resistance to standard platinum‑based chemotherapy. Treatment of patients with chemo‑resistant disease remains a clinical challenge. One mechanism of chemoresistance includes overexpression of pro‑survival proteins called inhibitors of apoptosis (IAP) which enable cancer cells to evade apoptosis. Due to their anti‑apoptotic activity, association with poor prognosis, and correlation with therapy resistance in multiple malignancies, IAP proteins have become an attractive target for development of anticancer therapeutics. Second mitochondrial activator of caspase (SMAC) mimetics are the most widely used IAP antagonists currently being tested in clinical trials as a monotherapy and in combination with different chemotherapeutic drugs to target different types of cancer. In the present study, the antitumor efficacy of combination therapy with birinapant, a bivalent SMAC mimetic compound, and carboplatin to target platinum‑resistant EOC cells was investigated. A 3D organoid bioassay was utilized to test the efficacy of the combination therapy in a panel of 7 EOC cell lines and 10 platinum‑resistant primary patient tumor samples. Findings from the in vitro studies demonstrated that the birinapant and carboplatin combination was effective in targeting a subset of ovarian cancer cell lines and platinum‑resistant primary patient tumor samples. This combination therapy was also effective in vitro and in vivo in targeting a platinum‑resistant patient‑derived xenograft (PDX) model established from one of the patient tumors tested. Overall, our study demonstrated that birinapant and carboplatin combination could target a subset of platinum‑resistant ovarian cancers and also highlights the potential of the 3D organoid bioassay as a preclinical tool to assess the response to chemotherapy or targeted therapies in ovarian cancer.

Dataset Information

Exploration of the sequential gene changes in epithelial ovarian cancer induced by carboplatin via microarray analysis.

Publications

Exploration of the sequential gene changes in epithelial ovarian cancer induced by carboplatin via microarray analysis.

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