Dissecting expression profiles of gastric precancerous lesions and early gastric cancer to explore crucial molecules in intestinal-type gastric cancer tumorigenesis.
Carcinoma in Situ
/ genetics
Cell Transformation, Neoplastic
/ genetics
Disease-Free Survival
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Lymphocytes, Tumor-Infiltrating
/ immunology
Macrophages
/ immunology
Neoplasm Grading
Neoplastic Stem Cells
/ pathology
Precancerous Conditions
/ genetics
Stomach Neoplasms
/ genetics
Transcriptome
Tumor Microenvironment
early gastric cancer
gastric precancerous lesions
gastric tumorigenesis
immune infiltration
prognosis
stemness
tumor hallmarks
Journal
The Journal of pathology
ISSN: 1096-9896
Titre abrégé: J Pathol
Pays: England
ID NLM: 0204634
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
18
09
2019
revised:
10
02
2020
accepted:
16
03
2020
pubmed:
25
3
2020
medline:
22
9
2020
entrez:
25
3
2020
Statut:
ppublish
Résumé
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 five 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 five-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. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Identifiants
pubmed: 32207854
doi: 10.1002/path.5434
pmc: PMC7317417
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
135-146Informations de copyright
© 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
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