ArticleClinical cancer research : an official journal of the American Association for Cancer Research2011
Genetic variation predicting cisplatin cytotoxicity associated with overall survival in lung cancer patients receiving platinum-based chemotherapy.
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, 2 of them syntheses that pooled it.
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Who cites it
70 citing papers in PubMed, 2 syntheses or guidelines pooled it, 109 citations in OpenAlex.
- Pooled it
- Meta-analysis on pharmacogenetics of platinum-based chemotherapy in non small cell lung cancer (NSCLC) patients.PloS one · 2012Pooled it
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- METTL Family in Healthy and Disease.Molecular biomedicine · 2024Review
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- PI3K/AKT pathway as a pivotal regulator of epithelial-mesenchymal transition in lung tumor cells.Cancer cell international · 2024Review
- YTHDF2 promotes gallbladder cancer progression and gemcitabine resistance via m6A-dependent DAPK3 degradation.Cancer science · 2023Article
- Integrative analysis of m3C associated genes reveals METTL2A as a potential oncogene in breast Cancer.Journal of translational medicine · 2022Article
- Downregulation of METTL6 mitigates cell progression, migration, invasion and adhesion in hepatocellular carcinoma by inhibiting cell adhesion molecules.International journal of oncology · 2022Article
- Crystal structure of human METTL6, the mCommunications biology · 2021Article
- Extending the lymphoblastoid cell line model for drug combination pharmacogenomics.Pharmacogenomics · 2021Review
- A metabolism-related gene signature for predicting the prognosis and therapeutic responses in patients with hepatocellular carcinoma.Annals of translational medicine · 2021Article
- A Call to Action: Dismantling Racial Injustices in Preclinical Research and Clinical Care of Black Patients Living with Small Cell Lung Cancer.Cancer discovery · 2021Article
- Induction of NEDD8-conjugating enzyme E2 UBE2F by platinum protects lung cancer cells from apoptosis and confers to platinum-insensitivity.Cell death & disease · 2020Article
10 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
purposeInherited variability in the prognosis of lung cancer patients treated with platinum-based chemotherapy has been widely investigated. However, the overall contribution of genetic variation to platinum response is not well established. To identify novel candidate single nucleotide polymorphisms (SNP)/genes, we carried out a genome-wide association study (GWAS) for cisplatin cytotoxicity by using lymphoblastoid cell lines (LCL), followed by an association study of selected SNPs from the GWAS with overall survival (OS) in lung cancer patients. EXPERIMENTAL
designA GWAS for cisplatin was conducted with 283 ethnically diverse LCLs. A total of 168 top SNPs were genotyped in 222 small cell lung cancer (SCLC) and 961 non-SCLC (NSCLC) patients treated with platinum-based therapy. Association of the SNPs with OS was determined by using the Cox regression model. Selected candidate genes were functionally validated by siRNA knockdown in human lung cancer cells.
resultsAmong 157 successfully genotyped SNPs, 9 and 10 SNPs were top SNPs associated with OS for patients with NSCLC and SCLC, respectively, although they were not significant after adjusting for multiple testing. Fifteen genes, including 7 located within 200 kb up or downstream of the 4 top SNPs and 8 genes for which expression was correlated with 3 SNPs in LCLs were selected for siRNA screening. Knockdown of DAPK3 and METTL6, for which expression levels were correlated with the rs11169748 and rs2440915 SNPs, significantly decreased cisplatin sensitivity in lung cancer cells.
conclusionsThis series of clinical and complementary laboratory-based functional studies identified several candidate genes/SNPs that might help predict treatment outcomes for platinum-based therapy of lung cancer.
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