Differential gene expression profiling of esophageal adenocarcinoma

Differential gene expression offers an attractive means by which to study genes that may be involved in disease development and/or progression. We performed quantitative gene expression in various stages of esophageal adenocarcinoma, treated exclusively by surgery with complete 2-field lymphadenectomy, in an attempt to discern genes involved in disease progression as well as genes that may predict survival.

Gene expression profiling was accomplished by cDNA-mediated annealing, selection, extension, and ligation (DASL) assay. RNA was extracted from 89 archived formalin-fixed, paraffin-embedded esophageal adenocarcinoma tissues. DASL assay was performed with the Sentrix Universal Array (Illumina Corp, San Diego, Calif) of 502 known cancer-related genes. Bioinformatics tools were used to determine significant differential gene expression in T1-2 versus T3-4 tumors and tumors without lymph node involvement (N0) versus tumors with lymph node involvement (N+). Gene expression was also correlated with overall survival.

Twenty-one genes were overexpressed in T1-2 compared with T3-4 tumors (false discovery rate of 0). Underexpression of 1 gene was seen in N+ compared with N0 tumors (false discovery rate of 0). For overall survival, underexpression of 9 genes correlated with long survival.

Using differential gene expression of 502 known cancer genes, we identified genes that may be involved at various stages in the progression of esophageal adenocarcinoma. We also identified genes that may correlate with prolonged survival and, thus, may serve as prognostic markers. These findings may provide further insight into the mechanisms of development and/or progression of esophageal adenocarcinoma. Prospective studies are needed to verify the prognostic value of these genes.