A gene expression signature of acquired chemoresistance to cisplatin and fluorouracil combination chemotherapy in gastric cancer patients

We initiated a prospective trial to identify transcriptional alterations associated with acquired chemotherapy resistance from pre- and post-biopsy samples from the same patient and uncover potential molecular pathways involved in treatment failure to help guide therapeutic alternatives. A prospecti...

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Bibliographic Details
Published in:PloS one 2011-02, Vol.6 (2), p.e16694
Main Authors: Kim, Hark Kyun, Choi, Il Ju, Kim, Chan Gyoo, Kim, Hee Sung, Oshima, Akira, Michalowski, Aleksandra, Green, Jeffrey E
Format: Article
Language:English
Subjects:
5-Fluorouracil
Adenocarcinoma - drug therapy
Adenocarcinoma - genetics
Adenocarcinoma - pathology
AKT1 protein
Analysis
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Apoptosis
Biology
Biopsy
Breast cancer
Cancer
Cancer therapies
Chemoresistance
Chemotherapy
Cisplatin
Cisplatin - administration & dosage
Clinical outcomes
Cluster Analysis
Clustering
Cytotoxicity
Dendritic cells
Deoxyribonucleic acid
DNA
DNA repair
Drug metabolism
Drug Resistance, Neoplasm - genetics
Embryonic stem cells
Endoscopy
Epidermal growth factor
Female
Fluorouracil
Fluorouracil - administration & dosage
Gastric cancer
Gene expression
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Genes
Genetics
Health aspects
High-Throughput Screening Assays
Humans
Laboratories
Leukemia
Male
Medical research
Medicine
Metabolism
Metastases
Middle Aged
Multiple myeloma
Neoplasm Metastasis
Pancreatic cancer
Patients
Physiological aspects
Prostate
Rodents
Stem cells
Stomach cancer
Stomach Neoplasms - drug therapy
Stomach Neoplasms - genetics
Stomach Neoplasms - pathology
TOR protein
Transcription
Tumors
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Summary:We initiated a prospective trial to identify transcriptional alterations associated with acquired chemotherapy resistance from pre- and post-biopsy samples from the same patient and uncover potential molecular pathways involved in treatment failure to help guide therapeutic alternatives. A prospective, high-throughput transcriptional profiling study was performed using endoscopic biopsy samples from 123 metastatic gastric cancer patients prior to cisplatin and fluorouracil (CF) combination chemotherapy. 22 patients who initially responded to CF were re-biopsied after they developed resistance to CF. An acquired chemotherapy resistance signature was identified by analyzing the gene expression profiles from the matched pre- and post-CF treated samples. The acquired resistance signature was able to segregate a separate cohort of 101 newly-diagnosed gastric cancer patients according to the time to progression after CF. Hierarchical clustering using a 633-gene acquired resistance signature (feature selection at P
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0016694