Genomewide mRNA profiling of esophageal squamous cell carcinoma for identification of cancer biomarkers

Abstract

Esophageal squamous cell carcinoma (ESCC) is a common cancer worldwide that has a poor survival rate among patients mainly because of lack of early markers to identify this cancer. Molecular mechanisms contributing to initiation and progression of esophageal squamous cell carcinoma are still poorly understood. Development of DNA microarrays technology allows high-throughput identification of gene expression profiles in cancers. In order to identify molecules as candidates for early diagnosis and/or therapeutic targets, we analyzed mRNA expression profiles of 20 surgically resected specimens of ESCC and compared them to their adjacent normal epithelium using whole genome DNA microarrays. We observed 119 genes significantly upregulated in ESCC samples as compared to the adjacent normal epithelium. The expression of two previously unreported overexpressed genes, ORAOV2 and FAP, was validated at the protein level by immunohistochemical labeling of tissue microarrays (TMAs) and archival tissue sections. Overexpression of ORAOV2 was observed in 116/118 (98%) of ESCC cases, while FAP overexpression was in 79/116 (68%) of cases. Osteopontin, which was identified in earlier studies, was observed to be upregulated in 114/118 (97%) cases. Overall, using this approach, we have identified a number of promising novel candidates that can be validated further for their potential to serve as biomarkers for ESCC.