The Whole Genome Expression Profiling And Immunohistochemical Expression Of GOS2and OSM In Gastric Intraepithelial Neoplasia And Early-stage Adenocarcinoma

Background:Unlike advanced-stage patients, patients with early-stage gastric adenocarcinoma(EGC) and precancerous lesions usually have no symptoms. It is important to understand more about EGC and precancerous lesions both clinically and biologically to improve the overall survival of patients with gastric carcinoma. Objectives:To explore the biological similarities and differences among high-and low-grade intraepithelial neoplasia(HGIN and LGIN, respectively), and EGC in detail, this study characterized their whole genome expression profiling to analyze the molecular and functional changes and discover related important genes in gastric early carcinogenesis. Together with the following evaluating of protein expression in tissues, this study would be a benefit for revealing of the early events in gastric carcinogenesis and provide some clue to related biomarker research. Methods:Gene expression profiling was performed on19LGIN,20HGIN,19EGC, and19gastritis tissue samples using microarrays. A GO(gene ontology) enrichment analysis was performed to explore the molecular distinction and functional correlation among these tissues. The differentially expressed genes, GO/G1switch2(GOS2) and Oncostatin M(OSM) were identified and their mRNA expression were validated using a real-time TaqMan(?) PCR assay with another group of independent tissue samples, including26LGIN,15HGIN,14EGC, and20gastritis. Furthermore, immunohistochemical(IHC) staining was used to detect GOS2and OSM expression in65cases chronic gastritis,45cases gastric intestinal metaplasia(IM),24cases LGIN,46cases HGIN,33cases EGC and18cases advanced-stage gastric adenocarcinoma(AGC). Results:The gene expression patterns of the LGIN and HGIN tissues and between LGIN and EGC were distinct. The related biological function were in the category of metabolism, defense response, and NF-kB cascade. The molecular differences between HGIN and EGC are not significant, which were mainly focused on the immune response. The mRNA expression and tissue expression after IHC staining of GOS2and OSM were relatively increased in HGIN and EGC. Conclusions:HGIN and LGIN are biologically distinct. Compared with LGIN, the biological similarities between HGIN and EGC were prominent. The overexpression of GOS2and OSM were validated as the neoplasia progressed from LGIN to HGIN, and then EGC. Alterations of metabolism and the immune response contribute to the malignant progression of gastric neoplasia, and maybe early events in gastric carcinogenesis.