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

Hyunki Kim; Jung Woo Eun j; Hanna Lee; Suk Woo Nam; Hwanseok Rhee; Kwi Hye Koh; Hoguen Kim

doi:10.1016/j.yexmp.2010.12.004

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

Hyunki Kim, Jung Woo Eun j, Hanna Lee, Suk Woo Nam, Hwanseok Rhee, Kwi Hye Koh, Hoguen Kim

Department of Pathology

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

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.

Original language	English
Pages (from-to)	201-209
Number of pages	9
Journal	Experimental and Molecular Pathology
Volume	90
Issue number	2
DOIs	https://doi.org/10.1016/j.yexmp.2010.12.004
State	Published - Apr 2011

Bibliographical note

Funding Information:
This study was supported by a faculty research grant of Yonsei University College of Medicine for 2008 ( 6-2008-0167 ), by FPR08A1-100 of the 21C Frontier Functional Proteomics Project from the Korean Ministry of Education, Science and Technology, and by the Converging Research Center Program through the Ministry of Education, Science and Technology ( 2010K001115 ).

Keywords

Gastric adenoma
Gastric carcinoma
Hydroxyprostaglandin dehydrogenase 15
Oligonucleotide microarray
Trefoil factor

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10.1016/j.yexmp.2010.12.004

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

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.",

keywords = "Gastric adenoma, Gastric carcinoma, Hydroxyprostaglandin dehydrogenase 15, Oligonucleotide microarray, Trefoil factor",

author = "Hyunki Kim and {Eun j}, {Jung Woo} and Hanna Lee and Nam, {Suk Woo} and Hwanseok Rhee and Koh, {Kwi Hye} and Hoguen Kim",

note = "Funding Information: This study was supported by a faculty research grant of Yonsei University College of Medicine for 2008 ( 6-2008-0167 ), by FPR08A1-100 of the 21C Frontier Functional Proteomics Project from the Korean Ministry of Education, Science and Technology, and by the Converging Research Center Program through the Ministry of Education, Science and Technology ( 2010K001115 ).",

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AU - Kim, Hyunki

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AU - Nam, Suk Woo

AU - Rhee, Hwanseok

AU - Koh, Kwi Hye

AU - Kim, Hoguen

N1 - Funding Information: This study was supported by a faculty research grant of Yonsei University College of Medicine for 2008 ( 6-2008-0167 ), by FPR08A1-100 of the 21C Frontier Functional Proteomics Project from the Korean Ministry of Education, Science and Technology, and by the Converging Research Center Program through the Ministry of Education, Science and Technology ( 2010K001115 ).

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N2 - 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.

AB - 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.

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KW - Oligonucleotide microarray

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

Abstract

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Keywords

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