Gene expression profiles in esophageal adenocarcinoma Peter S Dahlberg, MD, PhD, Lance F Ferrin, MD, PhD, Suzanne M Grindle, BS, Curtis M Nelson, BS, Chuong D Hoang, MD, Blake Jacobson, PhD  The Annals of Thoracic Surgery  Volume 77, Issue 3, Pages 1008-1015 (March 2004) DOI: 10.1016/j.athoracsur.2003.09.051

Fig 1 Unsupervised hierarchical clustering of samples. The cluster analysis was performed as a visualization tool to show that samples will cluster on the basis of their gene expression profiles into their expected pathological groups. The dendogram in the figure was generated using a set of 200 genes chosen by their ranking as defined by K group analysis. The K group analysis uses ANOVA and Kruskall Wallis tests to identify genes that are differentially expressed among samples. (ANOVA = analysis of variance; EAC = esophageal adenocarcinoma; SCCA = esophageal squamous cell carcinoma.) (Yellow box = esophageal adenocarcinoma; purple box = metastatic esophageal adenocarcinoma; light green box = esophageal adenocarcinoma cell line; dark green box = normal esophagus; maroon box = high-grade dysplasia; blue box = normal stomach; pink box = esophageal muscle and inflamed mucosa.) The Annals of Thoracic Surgery 2004 77, 1008-1015DOI: (10.1016/j.athoracsur.2003.09.051)

Fig 2 Paired analysis of gene expression in adenocarcinomas versus normal esophageal and normal gastric mucosal controls. At the p = 0.05 level, 1,891 genes showed differential levels of expression between esophageal adenocarcinoma samples and normal esophageal mucosa controls; 1,861 genes were differentially expressed between esophageal adenocarcinomas and normal gastric mucosa controls. The overlap of these two sets contained 369 genes. (EAC = esophageal adenocarcinoma; ESO = normal esophagus; STO = normal stomach.) The Annals of Thoracic Surgery 2004 77, 1008-1015DOI: (10.1016/j.athoracsur.2003.09.051)

Fig 3 Two-dimensional hierarchical cluster analysis. All tumors with matched normal tissue controls were used. Figure 2 describes how the subset of 369 genes used for the analysis was chosen. Gene ranking analysis was used to find the smallest group of genes that differentiates the experimental groups with the lowest error rate. With a 14% error rate, 64 genes were found to discriminate between tumor and normal tissue controls; this final set is displayed in the figure. (EAC = esophageal adenocarcinoma; ESO = normal esophagus; STO = normal stomach.) The Annals of Thoracic Surgery 2004 77, 1008-1015DOI: (10.1016/j.athoracsur.2003.09.051)

Fig 4 Induction of apoptosis pathway. GenMAPP is a computer application designed to visualize gene expression data on maps representing biological pathways. MappFinder is an accessory program to GenMAPP that analyzes pathways for statistically significant changes in gene expression using the percentages of genes changing, and then ranking the pathways from most to least changed. The induction of apoptosis pathway is shown as a representative example. The direction of gene expression changes in tumor samples would be expected to lead to less induction of apoptosis occurring in these cells. Genes underexpressed in esophageal adenocarcinoma specimens versus tissue from normal esophageal and gastric mucosa are highlighted in red; those overexpressed in tumors are highlighted in blue. (APAF-1 = apoptotic protease activating factor; BAX = BCL2-associated X protein; BCL2 = B-cell chronic lymphocytic leukemia/lymphoma 2; BCL-X = BCL2-like 1; BID = BH3 interacting domain death agonist; EAC = esophageal adenocarcinoma; FADD = FAS [TNFRSF6]-associated via death domain; FAS = tumor necrosis factor receptor superfamily, member 6 [TNFRSF6]; IKK = conserved helix-loop-helix ubiquitous kinase; JNKK = mitogen-activated protein kinase 4; MCL-1 = myeloid cell leukemia sequence 1; MDM-2 = transformed 3T3 cell double minute 2, p53 binding protein [mouse]; MEKK1 = mitogen-activated protein kinase 1; NF-kB = nuclear factor kB; NIK = mitogen-activated protein kinase 14; PARP = adenosine diphosthate-ribosyltransferase [NAD+; poly {ADP-ribose}] polymerase; RIP = human immunodeficiency virus-1 Rev binding protein; TNF = tumor necrosis factor; TNFR1 = tumor necrosis factor receptor 1; TNFR2 = tumor necrosis factor receptor 2; TNFRSF = tumor necrosis factor receptor superfamily; TRADD = TNFRSF1A-associated via death domain; TRAF1 = TNF receptor-associated factor 1; TRAF2 = TNF receptor-associated factor 2; TRAIL = tumor necrosis factor [ligand] superfamily, member 10 [TNFSF10].) The Annals of Thoracic Surgery 2004 77, 1008-1015DOI: (10.1016/j.athoracsur.2003.09.051)