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Prognostic biomarkers for esophageal adenocarcinoma identified by analysis of tumor transcriptome

Authors
 Soo Mi Kim  ;  Yun-Yong Park  ;  Eun Sung Park  ;  Jae Yong Cho  ;  Julie G. Izzo  ;  Di Zhang  ;  Sang-Bae Kim  ;  Jeffrey H. Lee  ;  Manoop S. Bhutani  ;  Stephen G. Swisher  ;  Xifeng Wu  ;  Kevin R. Coombes  ;  Dipen Maru  ;  Kenneth K. Wang  ;  Navtej S. Buttar  ;  Jaffer A. Ajani  ;  Ju-Seog Lee 
Citation
 PLOS ONE, Vol.5(11) : e15074, 2010 
Journal Title
 PLOS ONE 
Issue Date
2010
MeSH
Adenocarcinoma/diagnosis ; Adenocarcinoma/genetics* ; Adult ; Aged ; Biomarkers, Tumor/genetics* ; Cluster Analysis ; Esophageal Neoplasms/diagnosis ; Esophageal Neoplasms/genetics* ; Female ; Gene Expression Profiling* ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Multivariate Analysis ; Oligonucleotide Array Sequence Analysis/statistics & numerical data ; Osteonectin/genetics ; Osteopontin/genetics ; Prognosis ; Proportional Hazards Models ; Reverse Transcriptase Polymerase Chain Reaction
Abstract
BACKGROUND: Despite many attempts to establish pre-treatment prognostic markers to understand the clinical biology of esophageal adenocarcinoma (EAC), validated clinical biomarkers or parameters remain elusive. We generated and analyzed tumor transcriptome to develop a practical biomarker prognostic signature in EAC. METHODOLOGY/PRINCIPAL FINDINGS: Untreated esophageal endoscopic biopsy specimens were obtained from 64 patients undergoing surgery and chemoradiation. Using DNA microarray technology, genome-wide gene expression profiling was performed on 75 untreated cancer specimens from 64 EAC patients. By applying various statistical and informatical methods to gene expression data, we discovered distinct subgroups of EAC with differences in overall gene expression patterns and identified potential biomarkers significantly associated with prognosis. The candidate marker genes were further explored in formalin-fixed, paraffin-embedded tissues from an independent cohort (52 patients) using quantitative RT-PCR to measure gene expression. We identified two genes whose expression was associated with overall survival in 52 EAC patients and the combined 2-gene expression signature was independently associated with poor outcome (P<0.024) in the multivariate Cox hazard regression analysis. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that the molecular gene expression signatures are associated with prognosis of EAC patients and can be assessed prior to any therapy. This signature could provide important improvement for the management of EAC patients.
Files in This Item:
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DOI
10.1371/journal.pone.0015074
Appears in Collections:
5. Research Institutes (연구소) > Institute for Medical Convergence (연의-생공연 메디컬융합연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Park, Eun Sung(박은성)
Cho, Jae Yong(조재용) ORCID logo https://orcid.org/0000-0002-0926-1819
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/103093
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