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Dissecting expression profiles of gastric precancerous lesions and early gastric cancer to explore crucial molecules in intestinal-type gastric cancer tumorigenesis.

08:00 EDT 24th March 2020 | BioPortfolio

Summary of "Dissecting expression profiles of gastric precancerous lesions and early gastric cancer to explore crucial molecules in intestinal-type gastric cancer tumorigenesis."

Intestinal-type gastric cancer (IGC) has a clear and multistep histological evolution. No studies have comprehensively explored gastric tumorigenesis from inflammation through low-grade intraepithelial neoplasia (LGIN) and high-grade intraepithelial neoplasia (HGIN) to early gastric cancer (EGC). We sought to investigate the characteristics participating in IGC tumorigenesis and identify related prognostic information within the process. RNA expression profiles of 94 gastroscopic biopsies from 47 patients, including gastric precancerous lesions (
GPL:
LGIN and HGIN), EGC and paired controls, were detected by Agilent Microarray. During IGC tumorigenesis from LGIN through HGIN to EGC, the number of activity-changed tumor hallmarks increased. LGIN and HGIN had similar expression profiles when compared to EGC. We observed an increase in the stemness of gastric epithelial cells in LGIN, HGIN and EGC, and we found 27 consistent genes that might contribute to dedifferentiation, including 5 driver genes. Remarkably, we perceived that the immune microenvironment was more active in EGC than in GPL, especially in the infiltration of lymphocytes and macrophages. We identified a 5-gene signature from the gastric tumorigenesis process that could independently predict the overall survival and disease-free survival of GC patients (log rank test: p < 0.0001), and the robustness was verified in an independent cohort (n > 300) and by comparing with two established prognostic signatures in GC. In conclusion, during IGC tumorigenesis, cancer-like changes occur in LGIN and accumulate in HGIN and EGC. The immune microenvironment is more active in EGC than in LGIN and HGIN. The identified signature from the tumorigenesis process has robust prognostic significance for GC patients. This article is protected by copyright. All rights reserved.

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Name: The Journal of pathology
ISSN: 1096-9896
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