Abstract
BackgroundIntestinal metaplasia (IM) is a precursor lesion that precedes gastric cancer (GC). There are two IM histological subtypes, complete (CIM) and incomplete (IIM), the latter having higher progression rates to GC. This study was aimed at analysing gene expression and molecular processes involved in the progression from normal mucosa to IM, and also from IM subtypes to GC.MethodologyWe used expression data to compare the transcriptome of healthy gastric mucosa to that of IM not progressing to GC, and the transcriptome of IM subtypes that had progressed to GC to those that did not progress. Some deregulated genes were validated and pathway analyses were performed.ResultsComparison of IM subtypes that had progressed to GC with those that did not progress showed smaller differences in the expression profiles than the comparison of IM that did not progress with healthy mucosa. New transcripts identified in IM not progressing to GC included TRIM, TMEM, homeobox and transporter genes and SNORD116. Comparison to normal mucosa identified non tumoral Warburg effect and melatonin degradation as previously unreported processes involved in IM. Overexpressed antigen processing is common to both IM-subtypes progressing to GC, but IIM showed more over-expressed oncogenic genes and molecular processes than CIM.ConclusionsThere are greater differences in gene expression and molecular processes involved in the progression from normal healthy mucosa to IM than from IM to gastric cancer. While antigen processing is common in both IM-subtypes progressing to GC, more oncogenic processes are observed in the progression of IIM.
Highlights
Comparison of Intestinal metaplasia (IM) subtypes that had progressed to gastric cancer (GC) with those that did not progress showed smaller differences in the expression profiles than the comparison of IM that did not progress with healthy mucosa
There are greater differences in gene expression and molecular processes involved in the progression from normal healthy mucosa to IM than from IM to gastric cancer
While antigen processing is common in both IM-subtypes progressing to GC, more oncogenic processes are observed in the progression of IIM
Summary
Gastric carcinogenesis proceeds through a series of precursor lesions in the gastric mucosa named the Correas cascade, constituted by multi-atrophic gastritis, intestinal metaplasia (IM) and dysplasia conducting to gastric cancer (GC) [1]. In this process, IM is a crucial lesion, due to its high progression rate to GC (3.77/1000 person-years, in the province of Soria, Spain) [2]. IM is a trans-differentiation process of the gastric epithelium to an intestinal type, mostly induced by H.pylori infection and expression of the homeobox genes CDX1 and CDX2 It is a protective response against inflammation but it increases the risk of neoplastic transformation [3]. This study was aimed at analysing gene expression and molecular processes involved in the progression from normal mucosa to IM, and from IM subtypes to GC
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