Differential gene expression profiling of esophageal adenocarcinoma

Hammoud, Zane T.; Badve, Sunil; Zhao, Qianqian; Li, Lang; Saxena, Romil; Thorat, Mangesh A.; Morimiya, Akira; Rieger, Karen M.; Kesler, Kenneth A.

doi:10.1016/j.jtcvs.2008.08.052

« Previous Next »The Journal of Thoracic and Cardiovascular Surgery
Volume 137, Issue 4 , Pages 829-834, April 2009

Differential gene expression profiling of esophageal adenocarcinoma

Zane T. Hammoud, MD
- Department of Surgery, Thoracic Surgery Division, Indiana University School of Medicine, Indianapolis, Ind
- Address for reprints: Zane T. Hammoud, MD, Department of Surgery, Thoracic Surgery Division, Indiana University School of Medicine, 545 Barnhill Dr, EH 215, Indianapolis, IN 46202.
Sunil Badve, MD
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Ind
- Department of Internal Medicine, Indiana University School of Medicine, Indianapolis, Ind
- Translational Genomics Core of Indiana University Cancer Center, Indiana University School of Medicine, Indianapolis, Ind
Qianqian Zhao, MS
- Department of Bioinformatics, Indiana University School of Medicine, Indianapolis, Ind
Lang Li, PhD
- Department of Bioinformatics, Indiana University School of Medicine, Indianapolis, Ind
Romil Saxena, MD
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Ind
Mangesh A. Thorat, MD
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Ind
Akira Morimiya, BS
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Ind
Karen M. Rieger, MD
- Department of Surgery, Thoracic Surgery Division, Indiana University School of Medicine, Indianapolis, Ind
Kenneth A. Kesler, MD
- Department of Surgery, Thoracic Surgery Division, Indiana University School of Medicine, Indianapolis, Ind

Received 2 June 2008; received in revised form 24 July 2008; accepted 31 August 2008.

Background

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.

Methods

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.

Results

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.

Conclusions

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.

CTSNet classification: 7

Abbreviations and Acronyms: DASL, cDNA-mediated annealing, selection, extension, and ligation, DNA, deoxyribonucleic acid, FFPE, formalin-fixed, paraffin-embedded, RNA, ribonucleic acid