Differential gene-expression profiles associated with gastric adenoma

Abstract

Gastric adenomas may eventually progress to adenocarcinomas at varying rates. The purpose of the present study was to identify gene-expression profiles linked to the heterogeneous nature of gastric adenoma as compared to adenocarcinoma. Suppression subtractive hybridisation analysis was performed to extract relevant genes from two cases of low-and high-grade gastric adenomas. The identified genes were quantified by RT -PCR in 14 low-grade adenoma, nine high-grade adenoma and nine adenocarcinoma samples, followed by hierarchical clustering analysis to separate tumours into groups according to their gene-expression profiles. Nine genes previously implicated in carcinogenesis in a variety of organs, including three genes related to gastric adenocarcinoma, were identified. The overexpression of these genes in gastric adenoma has not been reported previously. The clustering analysis of these nine genes across 32 cases identified three groups, one of which consisted primarily of adenocarcinomas, whereas the other two groups consisted of adenomas. One group of adenomas, characterised by larger tumour size, exhibited gene-expression profiles of an intestinal cell lineage implicated in the pathogenesis of an intestinal-type gastric adenocarcinoma. Another adenoma group consisting of low-grade adenomas with smaller tumour size exhibited a unique expression profile. In conclusion, clustering analysis of expression profiles using a limited number of genes may serve as molecular markers for gastric adenoma with different biological properties. Although the prognostic values of these gene-expression profiles need to be evaluated in further follow-up study of adenoma cases, these findings add new insights to (a) our understanding of the pathogenesis of gastric tumours, (b) the development of specific tumour markers for clinical practice, and (c) the design of novel therapeutic targets.

Risk factors in malignant transformation of gastric epithelial neoplasia categorized by the revised Vienna classification: endoscopic, pathological, and immunophenotypic features

“…The removal of category 3 lesions (low-grade dysplasia), based on that classifi cation, is not necessary, whereas the removal of category 4 lesions (high-grade dysplasia and intramucosal cancer) is obligatory, because more than 80% of high-grade adenomas progress to adenocarcinomas [7]. However, there are frequently cases that do not easily fi t into the diagnostic categories; 15%-30% of low-grade adenomas progress to high-grade adenomas or adenocarcinomas [8,9]. Therefore, it is diffi cult for clinicians to determine which low-grade adenomas will progress.…”

Olfactomedin 4, a novel marker for the differentiation and progression of gastrointestinal cancers

“…OLFM4 protein expression has been observed in the oesophagus, stomach, small intestine and colon using immunohistochemistry [11]. In the recent years, increasing evidence indicates that OLFM4 is highly expressed in several types of tumors such as gastric [5,[12][13][14][15], pancreas [16], lung [16], breast [16] and colon [5,16,17] and is barely detectable in other tumors as well as in healthy tissues. OLFM4 expression is even related to tumor differentiation and progression and clinical course of diseases.…”

Comparative study of Western and Japanese criteria for biopsy-based diagnosis of gastric epithelial neoplasia

“…A number of previous studies have suggested that low-grade dysplasia (LGD) progresses to HGD [34][35][36][37], and that HGD becomes invasive GC within several months [38][39][40][41][42][43]. In 20-40 % of cases, diagnostic discrepancy between dysplasia evident at biopsy and GC observed in the resection specimen has been reported [34,37,44].…”