Differential gene expression profiling of esophageal adenocarcinoma
Zane Hammoud, Sunil Badve, Qianqian Zhao, Lang Li, Karen Rieger, Kenneth Kesler; Indiana University School of Medicine, Indianapolis, IN
Comment on this Abstract
Objective: Quantitative gene expression was performed on 89 esophageal adenocarcinomas, treated exclusively by surgery with complete 2 field lymphadenectomy, in an attempt to identify genes involved in disease development, progression, and survival.
Methods: RNA was extracted from archived formalin fixed, paraffin embedded tissue. Gene expression profiling was accomplished by the DASL (cDNA-mediated annealing, selection, extension, and ligation) assay using 502 known cancer genes. Differential gene expression was analyzed for T1-2(n=26) vs. T3-4(n=63) tumors and for tumors with lymph node involvement (LN+, n=66) vs. tumors without (LN-, n=23). Gene expression was also correlated with overall survival.
Results: Sixty-three genes were overexpressed in T1-2 compared with T3-4 tumors (21 genes had false discovery rate of 0). Overexpression of 16 genes and underexpression of 1 gene was seen in LN+ compared with LN- tumors (underexrpession of MYB gene had false discovery rate of 0). For overall survival, overexpression of 82 genes and underexpression of 8 genes correlated with prolonged survival (5 overexpressed and 2 underexpressed genes had false discovery rate of 0).
Conclusion: High-throughput gene expression profiling from archived tissue using DASL offers an attractive means of studying genetic alterations and pathways involved in tumor progression. Using differential gene expression of 502 known cancer genes, we identified genes that are involved at various stages in the progression of esophageal adenocarcinoma. We also identified genes that appear to correlate with prolonged survival and may serve as prognostic markers. Further studies are needed to verify and understand the role of these genes in the development and/or progression of esophageal adenocarcinoma.
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