ArticlePharmacogenetics and genomics2016
Genetic variations associated with gemcitabine treatment outcome in pancreatic cancer.
Article in Pharmacogenetics and genomics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
- Computational theranostics strategy for pancreatic ductal adenocarcinoma.Molecular diversity · 2026Article
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- Lymphocyte antigen 6 family member E suppresses apoptosis and promotes pancreatic cancer growth and migration via Wnt/β-catenin pathway activation.Scientific reports · 2024Article
- MICAL2 implies immunosuppressive features and acts as an independent and adverse prognostic biomarker in pancreatic cancer.Scientific reports · 2024Article
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- 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
- Effects of the Exposure of Human Non-Tumour Cells to Sera of Pancreatic Cancer Patients.Biomedicines · 2022Article
- Domination based classification algorithms for the controllability analysis of biological interaction networks.Scientific reports · 2022Article
- Development and validation of prognostic and diagnostic model for pancreatic ductal adenocarcinoma based on scRNA-seq and bulk-seq datasets.Human molecular genetics · 2022Article
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- Assessing equivalent and inverse change in genes between diverse experiments.Frontiers in bioinformatics · 2022Article
- Keratin 8 Is an Inflammation-Induced and Prognosis-Related Marker for Pancreatic Adenocarcinoma.Disease markers · 2022Article
- Machine learning-featured Secretogranin V is a circulating diagnostic biomarker for pancreatic adenocarcinomas associated with adipopenia.Frontiers in oncology · 2022Article
- Interferon alpha-inducible protein 27 (IFI27) is a prognostic marker for pancreatic cancer based on comprehensive bioinformatics analysis.Bioengineered · 2021Article
- Identification of novel hub genes and lncRNAs related to the prognosis and progression of pancreatic cancer by microarray and integrated bioinformatics analysis.Gland surgery · 2021Article
- Aberrant lactate dehydrogenase A signaling contributes metabolic signatures in pancreatic cancer.Annals of translational medicine · 2021Article
- ASF1B Promotes Oncogenesis in Lung Adenocarcinoma and Other Cancer Types.Frontiers in oncology · 2021Article
- TMPRSS4 Promotes Cell Proliferation and Inhibits Apoptosis in Pancreatic Ductal Adenocarcinoma by Activating ERK1/2 Signaling Pathway.Frontiers in oncology · 2021Article
- GPRC5A: An emerging prognostic biomarker for predicting malignancy of Pancreatic Cancer based on bioinformatics analysis.Journal of Cancer · 2021Article
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Authors and funding
10 authors.
Funding
Abstract
backgroundPancreatic cancer is a rapidly fatal disease with gemcitabine remaining the first-line therapy. We performed a genotype-phenotype association study to identify biomarkers for predicting gemcitabine treatment outcome. MATERIALS AND
methodsWe selected the top 200 single nucleotide polymorphisms (SNPs) identified from our previous genome-wide association study to associate with overall survival using 400 patients treated with/or without gemcitabine, followed by imputation analysis for regions around the identified SNPs and a replication study using an additional 537 patients by the TaqMan genotyping assay. Functional validation was performed using quantitative reverse transcription-PCR for gemcitabine-induced expression in genotyped lymphoblastoid cell lines and siRNA knockdown for candidate genes in pancreatic cancer cell lines.
resultsFour SNPs in chromosome 1, 3, 9, and 20 showed an interaction with gemcitabine from the discovery cohort of 400 patients (P<0.01). Subsequently, we selected those four genotyped plus four imputed SNPs for SNP×gemcitabine interaction analysis using the secondary validation cohort. Two imputed SNPs in CDH4 and KRT8P35 showed a trend in interaction with gemcitabine treatment. The lymphoblastoid cell lines with the variant sequences showed increased CDH4 expression compared with the wild-type cells after gemcitabine exposure. Knockdown of CDH4 significantly desensitized pancreatic cancer cells to gemcitabine cytotoxicity. The CDH4 SNPs that interacted with treatment are more predictive than prognostic.
conclusionWe identified SNPs with gemcitabine-dependent effects on overall survival. CDH4 might contribute to variations in gemcitabine response. These results might help us to better predict gemcitabine response in pancreatic cancer.
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