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pmid:29482638

Investigation of hypoxia networks in ovarian cancer via bioinformatics analysis.

Ke Zhang · Xiangjun Kong · Guangde Feng · Wei Xiang · Long Chen · Fang Yang · Chunyu Cao · Yifei Ding · Hang Chen · Mingxing Chu · Pingqing Wang · Baoyun Zhang

Journal of ovarian research · 2018 doi:10.1186/s13048-018-0388-x

Paper

complete

Experiment

complete

Data

partial

Analysis

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Execution

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title
Investigation of hypoxia networks in ovarian cancer via bioinformatics analysis.
doi
10.1186/s13048-018-0388-x
pmid
29482638
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[0]
Ke Zhang
[1]
Xiangjun Kong
[2]
Guangde Feng
[3]
Wei Xiang
[4]
Long Chen
[5]
Fang Yang
[6]
Chunyu Cao
[7]
Yifei Ding
[8]
Hang Chen
[9]
Mingxing Chu
[10]
Pingqing Wang
[11]
Baoyun Zhang
journal
Journal of ovarian research
year
2018
abstract
BACKGROUND: Ovarian cancer is a leading cause of the death from gynecologic malignancies. Hypoxia is closely related to the malignant growth of cells. However, the molecular mechanism of hypoxia-regulated ovarian cancer cells remains unclear. Thus, this study was conducted to identify the key genes and pathways implicated in the regulation of hypoxia by bioinformatics analysis. METHODS: Using the datasets of GSE53012 downloaded from the Gene Expression Omnibus (GEO), the differentially expressed genes (DEGs) were screened by comparing the RNA expression from cycling hypoxia group, chronic hypoxia group, and control group. Subsequently, cluster analysis was performed followed by the construction of the protein-protein interaction (PPI) network of the overlapping DEGs between the cycling hypoxia and chronic hypoxia using ClusterONE. In addition, gene ontology (GO) functional and pathway enrichment analyses of the DEGs in the most remarkable module were performed using Database for Annotation, Visualization and Integrated Discovery (DAVID) software. Ultimately, the signaling pathways associated with hypoxia were verified by RT-PCR, WB, and MTT assays. RESULTS: A total of 931 overlapping DEGs were identified. Nine hub genes and seven node genes were screened by analyzing the PPI and pathway integration networks, including ESR1, MMP2, ErbB2, MYC, VIM, CYBB, EDN1, SERPINE1, and PDK. Additionally, 11 key pathways closely associated with hypoxia were identified, including focal adhesion, ErbB signaling, and proteoglycans in cancer, among which the ErbB signaling pathway was verified by RT-PCR, WB, and MTT assays. Furthermore, functional enrichment analysis revealed that these genes were mainly involved in the proliferation of ovarian cancer cells, such as regulation of cell proliferation, cell adhesion, positive regulation of cell migration, focal adhesion, and extracellular matrix binding. CONCLUSION: The results show that hypoxia can promote the proliferation of ovarian cancer cells by affecting the invasion and adhesion functions through the dysregulation of ErbB signaling, which may be governed by the HIF-1α-TGFA-EGFR-ErbB2-MYC axis. These findings will contribute to the identification of new targets for the diagnosis and treatment of ovarian cancer.
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Statistical significance was assessed by one-way ANOVA followed by Tukey’s multiple comparisons test using Prism statistical software (GraphPad Software, Inc., La Jolla, CA), with differences considered significant at the level of P < .05.
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Expression data from three human cancer cell lines (PC-3, SK-OV-3, WM793B) exposed to experimental cycling and chronic hypoxa in vitro
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ith hypoxia were verified by RT-PCR, WB, and MTT assays. RESULTS: A total of 931 overlapping
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{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:29482638", "kind": "science-record", "revision": 8, "content_hash": "sha256:0071014943f3ecefa8c7de45767d06a505b1a566498e587b9ef239628cbf56f5", "created_at": "2026-11-01T15:40:31Z", "updated_at": "2026-11-01T22:43:17Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Investigation of hypoxia networks in ovarian cancer via bioinformatics analysis.", "doi": "10.1186/s13048-018-0388-x", "pmid": "29482638", "authors": ["Ke Zhang", "Xiangjun Kong", "Guangde Feng", "Wei Xiang", "Long Chen", "Fang Yang", "Chunyu Cao", "Yifei Ding", "Hang Chen", "Mingxing Chu", "Pingqing Wang", "Baoyun Zhang"], "journal": "Journal of ovarian research", "year": 2018, "abstract": "BACKGROUND: Ovarian cancer is a leading cause of the death from gynecologic malignancies. Hypoxia is closely related to the malignant growth of cells. However, the molecular mechanism of hypoxia-regulated ovarian cancer cells remains unclear. Thus, this study was conducted to identify the key genes and pathways implicated in the regulation of hypoxia by bioinformatics analysis.\nMETHODS: Using the datasets of GSE53012 downloaded from the Gene Expression Omnibus (GEO), the differentially expressed genes (DEGs) were screened by comparing the RNA expression from cycling hypoxia group, chronic hypoxia group, and control group. Subsequently, cluster analysis was performed followed by the construction of the protein-protein interaction (PPI) network of the overlapping DEGs between the cycling hypoxia and chronic hypoxia using ClusterONE. In addition, gene ontology (GO) functional and pathway enrichment analyses of the DEGs in the most remarkable module were performed using Database for Annotation, Visualization and Integrated Discovery (DAVID) software. Ultimately, the signaling pathways associated with hypoxia were verified by RT-PCR, WB, and MTT assays.\nRESULTS: A total of 931 overlapping DEGs were identified. Nine hub genes and seven node genes were screened by analyzing the PPI and pathway integration networks, including ESR1, MMP2, ErbB2, MYC, VIM, CYBB, EDN1, SERPINE1, and PDK. Additionally, 11 key pathways closely associated with hypoxia were identified, including focal adhesion, ErbB signaling, and proteoglycans in cancer, among which the ErbB signaling pathway was verified by RT-PCR, WB, and MTT assays. Furthermore, functional enrichment analysis revealed that these genes were mainly involved in the proliferation of ovarian cancer cells, such as regulation of cell proliferation, cell adhesion, positive regulation of cell migration, focal adhesion, and extracellular matrix binding.\nCONCLUSION: The results show that hypoxia can promote the proliferation of ovarian cancer cells by affecting the invasion and adhesion functions through the dysregulation of ErbB signaling, which may be governed by the HIF-1α-TGFA-EGFR-ErbB2-MYC axis. 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