ArticleThe Journal of pathology2012
Low MAD2 expression levels associate with reduced progression-free survival in patients with high-grade serous epithelial ovarian cancer.
Article in The Journal of pathology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 75 citations in OpenAlex.
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- TRIP13: A promising cancer immunotherapy target.Cancer innovation · 2024Review
- Role of TRIP13 in human cancer development.Molecular biology reports · 2024Review
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- MAD2 activates IGF1R/PI3K/AKT pathway and promotes cholangiocarcinoma progression by interfering USP44/LIMA1 complex.Oncogene · 2023Article
- Targeting TRIP13 for overcoming anticancer drug resistance (Review).Oncology reports · 2023Article
- The positive feedback loop of MAD2L1/TYK2/STAT3 induces progression in B-cell acute lymphoblastic leukaemia.Journal of cancer research and clinical oncology · 2023Article
- Through the Looking Glass: Updated Insights on Ovarian Cancer Diagnostics.Diagnostics (Basel, Switzerland) · 2023Review
- Predicting Prognosis and Platinum Resistance in Ovarian Cancer: Role of Immunohistochemistry Biomarkers.International journal of molecular sciences · 2023Review
- ROS and miRNA Dysregulation in Ovarian Cancer Development, Angiogenesis and Therapeutic Resistance.International journal of molecular sciences · 2022Review
- Mitotic checkpoint defects: en route to cancer and drug resistance.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2021Review
- Article
- Identification of Core Genes and Pathways in Medulloblastoma by Integrated Bioinformatics Analysis.Journal of molecular neuroscience : MN · 2020Article
- Identification of Hub Genes in High-Grade Serous Ovarian Cancer Using Weighted Gene Co-Expression Network Analysis.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- Article
- Transcriptome analysis reveals key signature genes involved in the oncogenesis of lung cancer.Cancer biomarkers : section A of Disease markers · 2020Article
- The HuR CMLD-2 inhibitor exhibits antitumor effects via MAD2 downregulation in thyroid cancer cells.Scientific reports · 2019Article
- Aneuploidy: Cancer strength or vulnerability?International journal of cancer · 2019Review
- Insights into a Crucial Role of TRIP13 in Human Cancer.Computational and structural biotechnology journal · 2019Review
- Elevated TRIP13 drives cell proliferation and drug resistance in bladder cancer.American journal of translational research · 2019Article
Corrections and comments
- Erratum issued
Authors and funding
17 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epithelial ovarian cancer (EOC) has an innate susceptibility to become chemoresistant. Up to 30% of patients do not respond to conventional chemotherapy [paclitaxel (Taxol®) in combination with carboplatin] and, of those who have an initial response, many patients relapse. Therefore, an understanding of the molecular mechanisms that regulate cellular chemotherapeutic responses in EOC cells has the potential to impact significantly on patient outcome. The mitotic arrest deficiency protein 2 (MAD2), is a centrally important mediator of the cellular response to paclitaxel. MAD2 immunohistochemical analysis was performed on 82 high-grade serous EOC samples. A multivariate Cox regression analysis of nuclear MAD2 IHC intensity adjusting for stage, tumour grade and optimum surgical debulking revealed that low MAD2 IHC staining intensity was significantly associated with reduced progression-free survival (PFS) (p = 0.0003), with a hazard ratio of 4.689. The in vitro analyses of five ovarian cancer cell lines demonstrated that cells with low MAD2 expression were less sensitive to paclitaxel. Furthermore, paclitaxel-induced activation of the spindle assembly checkpoint (SAC) and apoptotic cell death was abrogated in cells transfected with MAD2 siRNA. In silico analysis identified a miR-433 binding domain in the MAD2 3' UTR, which was verified in a series of experiments. Firstly, MAD2 protein expression levels were down-regulated in pre-miR-433 transfected A2780 cells. Secondly, pre-miR-433 suppressed the activity of a reporter construct containing the 3'-UTR of MAD2. Thirdly, blocking miR-433 binding to the MAD2 3' UTR protected MAD2 from miR-433 induced protein down-regulation. Importantly, reduced MAD2 protein expression in pre-miR-433-transfected A2780 cells rendered these cells less sensitive to paclitaxel. In conclusion, loss of MAD2 protein expression results in increased resistance to paclitaxel in EOC cells. Measuring MAD2 IHC staining intensity may predict paclitaxel responses in women presenting with high-grade serous EOC.
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