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Gene expression changes in patient-matched gastric normal mucosa, adenomas, and carcinomas

Authors
 Hyunki Kim  ;  Jung Woo Eun  ;  Hanna Lee  ;  Suk Woo Nam  ;  Hwanseok Rhee  ;  Kwi Hye Koh  ;  Hoguen Kim 
Citation
 EXPERIMENTAL AND MOLECULAR PATHOLOGY, Vol.90(2) : 201-209, 2011 
Journal Title
EXPERIMENTAL AND MOLECULAR PATHOLOGY
ISSN
 0014-4800 
Issue Date
2011
MeSH
Adenoma/enzymology ; Adenoma/genetics* ; Adenoma/pathology ; Aged ; Aged, 80 and over ; Carcinoma/enzymology ; Carcinoma/genetics* ; Carcinoma/pathology ; Cluster Analysis ; Down-Regulation/genetics ; Female ; Gastric Mucosa/enzymology ; Gastric Mucosa/metabolism* ; Gastric Mucosa/pathology ; Gene Expression Profiling* ; Gene Expression Regulation, Neoplastic* ; Genes, Neoplasm/genetics ; Humans ; Hydroxyprostaglandin Dehydrogenases/genetics ; Hydroxyprostaglandin Dehydrogenases/metabolism ; Immunohistochemistry ; Male ; Middle Aged ; Peptides/genetics ; Peptides/metabolism ; Reproducibility of Results ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction/genetics ; Stomach Neoplasms/enzymology ; Stomach Neoplasms/genetics* ; Stomach Neoplasms/pathology ; Trefoil Factor-2 ; Up-Regulation/genetics
Keywords
Gastric adenoma ; Gastric carcinoma ; Oligonucleotide microarray ; Trefoil factor ; Hydroxyprostaglandin dehydrogenase 15
Abstract
A subset of gastric carcinomas shows histologic evidence of a multistep process, progressing from gastric adenoma to gastric carcinoma. We examined gene expression changes during the gastric adenoma-carcinoma sequence in 26 snap-frozen samples (normal mucosa, adenoma, and carcinoma samples from eight patients and two additional carcinomas) by oligonucleotide microarray. Unsupervised hierarchical clustering analysis demonstrated differential gene expression between gastric normal mucosa, adenomas and carcinomas. We identified 319 and 422 genes differentially regulated in adenoma and carcinoma, respectively, relative to normal mucosa, using a combination of Welch's t-test and fold-change analysis. Applying a combination of robust multi-category support vector machines to the data, reveal that 39 and 21 genes were gradually up- and down-regulated, respectively, in succession in normal mucosa, adenoma, and carcinoma samples. We validated gene expression levels of four genes: hydroxyprostaglandin dehydrogenase 15 (HPGD), follistatin-like 1, trefoil factor 1 (TTF1) and trefoil factor 2 (TFF2) by RT-PCR and found direct correlation with microarray results. The expressions of the TFF2 and HPGD genes were further evaluated by immunohistochemistry in 103 adenomas and 70 carcinomas; expression of both proteins was decreased in these tissues. The progressive alteration in gene expression in the transition from normal mucosa to carcinoma suggests that these changes may play critical roles in gastric carcinogenesis.
Full Text
http://www.sciencedirect.com/science/article/pii/S0014480010001681
DOI
10.1016/j.yexmp.2010.12.004
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pediatrics (소아과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hyunki(김현기) ORCID logo https://orcid.org/0000-0003-2292-5584
Kim, Hogeun(김호근)
Rhee, Hwan Seok(이환석)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/92736
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