Expression Profile of Malignant and Nonmalignant Lesions of Esophagus and Stomach: Differential Activity of Functional Modules Related to Inflammation and Lipid Metabolism

Abstract

Adenocarcinomas of stomach and esophagus are frequently associated with preceding inflammatory alterations of the normal mucosa. Whereas intestinal metaplasia of the gastric mucosa is associated with higher risk of malignization, Barrett's disease is a risk factor for adenocarcinoma of the esophagus. Barrett's disease is characterized by the substitution of the squamous mucosa of the esophagus by a columnar tissue classified histopathologically as intestinal metaplasia. Using cDNA microarrays, we determined the expression profile of normal gastric and esophageal mucosa as well as intestinal metaplasia and adenocarcinomas from both organs. Data were explored to define functional alterations related to the transformation from squamous to columnar epithelium and the malignant transformation from intestinal metaplasia to adenocarcinomas. Based on their expression profile, adenocarcinomas of the esophagus showed stronger correlation with intestinal metaplasia of the stomach than with Barrett's mucosa. Second, we identified two functional modules, lipid metabolism and cytokine, as being altered with higher statistical significance. Whereas the lipid metabolism module is active in samples representing intestinal metaplasia and inactive in adenocarcinomas, the cytokine module is inactive in samples representing normal esophagus and esophagitis. Using the concept of relevance networks, we determined the changes in linear correlation of genes pertaining to these two functional modules. Exploitation of the data presented herein will help in the precise molecular characterization of adenocarcinoma from the distal esophagus, avoiding the topographical and descriptive classification that is currently adopted, and help with the proper management of patients with Barrett's disease. (Cancer Res 2005; 65(16): 7127-36)

Deregulated expression of fat and muscle genes in B-cell chronic lymphocytic leukemia with high lipoprotein lipase expression

“…Such 'gene set enrichement analysis' allows for the discovery of gene sets that might function in an LPL expression profiling in B-CLL M Bilban et al orchestrated manner that would not be revealed otherwise. 45,54 The two top-scoring pathways identified suggest metabolic (fatty acid degradation) as well as cell plasticity (MTA3 signaling) related adaptations of LPL þ CLL (Figure 4 and Supplemental Table 4). Further evidence for extensive reprogramming of gene expression in LPL þ CLL comes from analysis of the LPL þ signature in 52 tissues: we reasoned that a tissue's phenotype is related to the LPL þ phenotype if the expression levels of the LPL þ signature genes in the (potentially related) tissue significantly differ from the mean expression over all tissues.…”

“…Differential activity of lipid metabolism has recently been described for adenocarcinomas of the stomach. 54 It is well recognized that the cytoskeleton is involved in cell transformation. 57 (iii) Different stages of differentiation at the moment of malignant transformation or a certain degree of plasticity or cell reprogramming.…”

EPO-R Expression Patterns in Resected Gastric Adenocarcinoma Followed by Adjuvant Chemoradiation Treatment

“…Recently, a number of published studies have characterized by the use of microarrays that try to define different expression profiles with prognostic value and useful for predicting treatment response. However, among the selected genes, Epo or Epo-R gene have not been included in these studies [22][23][24][25][26][27][28].…”

Mechanisms of Barrett's oesophagus: Intestinal differentiation, stem cells, and tissue models

“…gastric and duodenal) mucosa and BE but stark differences between the squamous normal esophageal tissues and BE. Amongst genes relatively specific to BE are CK8, CK20, MUC2, MUC5AC, MUC6 and mucin-associated trefoil factors TFF1, TFF2 and TFF3 (11, 12). Analyzing multiple datasets from six independent studies several transcription factors (CDX1, CDX2, HNF1, and HNF4) and the TGF-β/BMP pathway have been identified being significantly enriched in BE (13).…”