Background: To screen key molecules to aid the prediction of prognosis of patients with esophageal cancer, we have previously reported gene-expression profiling in esophageal cancer. The expressions of a variety of genes related to cell cycle, gene-repair, tumor invasion, apoptosis and chemoradiotherapy resistance were up-regulated in the poor prognostic cluster. In the current study, the protein expression patterns of these genes within esophageal cancer cells were examined immunohistochemically to determine their relation to clinicopathologic findings and disease recurrence-free survival of patients.
Methods: Using oligonucleotide microarrays, we analysed total RNA expression levels corresponding to 12,600 transcript sequences in 24 paired cancerous and normal tissues obtained by operative specimens from 12 patients with esophageal squamous cell carcinoma. Hierarchical clustering analysis was performed using Spotfire software version 7.0. Tissue samples from 101 patients with esophageal squamous cell carcinoma were prepared for immunohistochemical analysis.
Results: Hierarchical clustering analysis using gene expression ratios (cancer/normal) divided the 12 patients into 2 groups; all 7 patients in the 1st cluster survived without relapse, whereas all 5 patients in the 2nd cluster relapsed (log-rank test: p = 0.006). The expression of a variety of genes including endothelin (ET), CD147, MMP-2 and SUMO-1 was up-regulated in the poor prognostic cluster. The expression of ET, CD147 and MMP-2 protein was related to reduced relapse-free survival.
Conclusion: These results suggest that gene-expression profiling may be useful to detect favorable prognostic factors in patients with esophageal squamous cell carcinoma.