ArticlePloS one2013
Contribution of FKBP5 genetic variation to gemcitabine treatment and survival in pancreatic adenocarcinoma.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Interaction between early-life stress and FKBP5 gene variants in major depressive disorder and post-traumatic stress disorder: A systematic review and meta-analysis.Journal of affective disorders · 2018Pooled it
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- MICAL2 implies immunosuppressive features and acts as an independent and adverse prognostic biomarker in pancreatic cancer.Scientific reports · 2024Article
- Identification of the Genetic Association Between Type-2-Diabetes and Pancreatic Cancer.Biochemical genetics · 2023Article
- Imatinib facilitates gemcitabine sensitivity by targeting epigenetically activated PDGFC signaling in pancreatic cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- FASN multi-omic characterization reveals metabolic heterogeneity in pancreatic and prostate adenocarcinoma.Journal of translational medicine · 2023Article
- The Scaffold Immunophilin FKBP51 Is a Phosphoprotein That Undergoes Dynamic Mitochondrial-Nuclear Shuttling.Cells · 2022Article
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- Domination based classification algorithms for the controllability analysis of biological interaction networks.Scientific reports · 2022Article
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- Assessing equivalent and inverse change in genes between diverse experiments.Frontiers in bioinformatics · 2022Article
- Interferon alpha-inducible protein 27 (IFI27) is a prognostic marker for pancreatic cancer based on comprehensive bioinformatics analysis.Bioengineered · 2021Article
- An Integrated Data Analysis of mRNA, miRNA and Signaling Pathways in Pancreatic Cancer.Biochemical genetics · 2021Article
- Stress-Responsive Gene FK506-Binding Protein 51 Mediates Alcohol-Induced Liver Injury Through the Hippo Pathway and Chemokine (C-X-C Motif) Ligand 1 Signaling.Hepatology (Baltimore, Md.) · 2021Article
- ADAM9-Responsive Mesoporous Silica Nanoparticles for Targeted Drug Delivery in Pancreatic Cancer.Cancers · 2021Article
- Extending the lymphoblastoid cell line model for drug combination pharmacogenomics.Pharmacogenomics · 2021Review
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
purposeFKBP51, (FKBP5), is a negative regulator of Akt. Variability in FKBP5 expression level is a major factor contributing to variation in response to chemotherapeutic agents including gemcitabine, a first line treatment for pancreatic cancer. Genetic variation in FKBP5 could influence its function and, ultimately, treatment response of pancreatic cancer. EXPERIMENTAL
designWe set out to comprehensively study the role of genetic variation in FKBP5 identified by Next Generation DNA resequencing on response to gemcitabine treatment of pancreatic cancer by utilizing both tumor and germline DNA samples from 43 pancreatic cancer patients, including 19 paired normal-tumor samples. Next, genotype-phenotype association studies were performed with overall survival as well as with FKBP5 gene expression in tumor using the same samples in which resequencing had been performed, followed by functional genomics studies.
resultsIn-depth resequencing identified 404 FKBP5 single nucleotide polymorphisms (SNPs) in normal and tumor DNA. SNPs with the strongest associations with survival or FKBP5 expression were subjected to functional genomic study. Electromobility shift assay showed that the rs73748206 "A(T)" SNP altered DNA-protein binding patterns, consistent with significantly increased reporter gene activity, possibly through its increased binding to Glucocorticoid Receptor (GR). The effect of rs73748206 was confirmed on the basis of its association with FKBP5 expression by affecting the binding to GR in lymphoblastoid cell lines derived from the same patients for whom DNA was used for resequencing.
conclusionThis comprehensive FKBP5 resequencing study provides insights into the role of genetic variation in variation of gemcitabine response.
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