Gene Expression Study and Pathway Analysis of Histological Subtypes of Intestinal Metaplasia that Progress to Gastric Cancer

Background Intestinal 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. Methodology We 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. Results Comparison 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. Conclusions 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.Fondo de investigaciones Sanitarias del Institute de Salud Carlos III, Spanish Ministry of Health. Cofounded by European Regional Development Funds (ERDF/FEDER) "A way to build Europe". http://www.isciii.es/. Grant numbers: PI03/0077 (CAG) PI10/01089 (CAG), PI10/01031 (JG), PI10/01203 (JMS) RETICC RD12/0036/0018 (CAG, NS, OC, NG). Agenda de Gestio d'Ajuts Universitaris i de Recerca (AGAUR), Generalitat de Catalunya, Catalunya, Spain. http://agaur.gencat.cat/en/inici/index.html. Grant number: exp. 2014 SGR 726 (CAG, OC, NG, NS). Institut d'Investigacio Biomedica de Bellvitge (IDIBELL), http://www.idibell.cat/en, PhD scholarship to OC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript