ArticleClinical cancer research : an official journal of the American Association for Cancer Research2011
BAD phosphorylation determines ovarian cancer chemosensitivity and patient survival.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 1 of them a synthesis that pooled it.
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Who cites it
70 citing papers in PubMed, 1 synthesis or guideline pooled it, 109 citations in OpenAlex.
- Increased expression of TET3 predicts unfavorable prognosis in patients with ovarian cancer-a bioinformatics integrative analysis.Journal of ovarian research · 2019Pooled it
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- Platinum-resistant ovarian cancer: From mechanisms to treatment strategies.Genes & diseases · 2026Review
- Integration of Bulk and Single-Cell RNA Sequencing to Identify RNA Modifications-Related Prognostic Signature in Ovarian Cancer.International journal of general medicine · 2025Article
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- Comprehensive analysis of consensus molecular subtypes for ovarian cancer from bulk to single-cell perspectives.The Journal of biological chemistry · 2024Article
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- Prognostic value of regulatory T cells and T helper 17 cells in high grade serous ovarian carcinoma.Journal of cancer research and clinical oncology · 2023Article
- A ribosomal gene panel predicting a novel synthetic lethality in non-BRCAness tumors.Signal transduction and targeted therapy · 2023Article
- A chemotherapy response prediction model derived from tumor-promoting B and Tregs and proinflammatory macrophages in HGSOC.Frontiers in oncology · 2023Article
- FBP1 knockdown decreases ovarian cancer formation and cisplatin resistance through EZH2-mediated H3K27me3.Bioscience reports · 2022Article
- Single-cell characterization of step-wise acquisition of carboplatin resistance in ovarian cancer.NPJ systems biology and applications · 2022Article
- Dissecting Tissue Compartment-Specific Protein Signatures in Primary and Metastatic Oropharyngeal Squamous Cell Carcinomas.Frontiers in immunology · 2022Article
- Overexpression of transmembrane protein 102 implicates poor prognosis and chemoresistance in epithelial ovarian carcinoma patients.American journal of cancer research · 2022Article
- Identification of a Gene Signature of Cancer-Associated Fibroblasts to Predict Prognosis in Ovarian Cancer.Frontiers in genetics · 2022Article
- Combined inhibition of BADSer99 phosphorylation and PARP ablates models of recurrent ovarian carcinoma.Communications medicine · 2022Article
- Identification of a Recurrence Gene Signature for Ovarian Cancer Prognosis by Integrating Single-Cell RNA Sequencing and Bulk Expression Datasets.Frontiers in genetics · 2022Article
10 more citing papers are in PubMed but not listed here.
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Authors and funding
24 authors at 5 institutions in 2 countries.
Funding
Abstract
purposeDespite initial sensitivity to chemotherapy, ovarian cancers (OVCA) often develop drug resistance, which limits patient survival. Using specimens and/or genomic data from 289 patients and a panel of cancer cell lines, we explored genome-wide expression changes that underlie the evolution of OVCA chemoresistance and characterized the BCL2 antagonist of cell death (BAD) apoptosis pathway as a determinant of chemosensitivity and patient survival. EXPERIMENTAL
designSerial OVCA cell cisplatin treatments were performed in parallel with measurements of genome-wide expression changes. Pathway analysis was carried out on genes associated with increasing cisplatin resistance (EC(50)). BAD-pathway expression and BAD protein phosphorylation were evaluated in patient samples and cell lines as determinants of chemosensitivity and/or clinical outcome and as therapeutic targets.
resultsInduced in vitro OVCA cisplatin resistance was associated with BAD-pathway expression (P < 0.001). In OVCA cell lines and primary specimens, BAD protein phosphorylation was associated with platinum resistance (n = 147, P < 0.0001) and also with overall patient survival (n = 134, P = 0.0007). Targeted modulation of BAD-phosphorylation levels influenced cisplatin sensitivity. A 47-gene BAD-pathway score was associated with in vitro phosphorylated BAD levels and with survival in 142 patients with advanced-stage (III/IV) serous OVCA. Integration of BAD-phosphorylation or BAD-pathway score with OVCA surgical cytoreductive status was significantly associated with overall survival by log-rank test (P = 0.004 and P < 0.0001, respectively).
conclusionThe BAD apoptosis pathway influences OVCA chemosensitivity and overall survival, likely via modulation of BAD phosphorylation. The pathway has clinical relevance as a biomarker of therapeutic response, patient survival, and as a promising therapeutic target.
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