Gene Expression Profiling of Metaplastic Lineages Identifies CDH17 as a Prognostic Marker in Early Stage Gastric Cancer

Hyuk Joon Lee, KiTaek Nam, Heae Surng Park, Min A. Kim, Bonnie J. LaFleur, Hiroyuki Aburatani, Han Kwang Yang, Woo Ho Kim, James R. Goldenring

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Abstract

Background & Aims: Intestinal metaplasia (IM) and spasmolytic polypeptide-expressing metaplasia (SPEM) are precursors to gastric carcinogenesis. We sought to identify molecular biomarkers of gastric metaplasias and gastric cancer by gene expression profiling of metaplastic lesions from patients. Methods: Complementary DNA microarray analysis was performed on IM and SPEM cells isolated from patient samples using laser capture microdissection. Up-regulated transcripts in metaplastic lesions were confirmed by immunostaining analysis in IM, SPEM, and gastric cancer tissues. Proteins that were highly expressed specifically in gastric cancer tissues were analyzed for their association with survival in a test set (n = 450) and a validation set (n = 502) of samples from gastric cancer patients. Results: Compared with normal chief cells, 858 genes were differentially expressed in IM or SPEM samples. Immunostaining was detected for 12 proteins, including 3 new markers of IM (ACE2, LGALS4, AKR1B10) and 3 of SPEM (OLFM4, LYZ, DPCR1). Of 13 proteins expressed in IM or SPEM, 8 were expressed by 17%-50% of human gastric cancer tissues (MUC13, OLFM4, CDH17, KRT20, MUC5AC, LGALS4, AKR1B10, REG4). Expression of CDH17 or MUC13 correlated with patient survival in the test and validation sets. Multivariate analysis showed that CDH17 was an independent prognostic factor in patients with stage I or node-negative disease. Conclusions: We identified several novel biomarkers for IM, SPEM, and gastric cancer using gene expression profiling of human metaplastic lesions. Expression of CDH17 and MUC13 was up-regulated in gastric cancer tissues. CDH17 is a promising prognostic marker for early stage gastric cancer.

Original languageEnglish
JournalGastroenterology
Volume139
Issue number1
DOIs
Publication statusPublished - 2010 Jan 1

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Metaplasia
Gene Expression Profiling
Stomach Neoplasms
Galectin 4
Neoplasm Genes
Stomach
Biomarkers
Laser Capture Microdissection
Proteins
Survival
Microarray Analysis
spasmolytic polypeptide
Oligonucleotide Array Sequence Analysis

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

Cite this

Lee, Hyuk Joon ; Nam, KiTaek ; Park, Heae Surng ; Kim, Min A. ; LaFleur, Bonnie J. ; Aburatani, Hiroyuki ; Yang, Han Kwang ; Kim, Woo Ho ; Goldenring, James R. / Gene Expression Profiling of Metaplastic Lineages Identifies CDH17 as a Prognostic Marker in Early Stage Gastric Cancer. In: Gastroenterology. 2010 ; Vol. 139, No. 1.
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title = "Gene Expression Profiling of Metaplastic Lineages Identifies CDH17 as a Prognostic Marker in Early Stage Gastric Cancer",
abstract = "Background & Aims: Intestinal metaplasia (IM) and spasmolytic polypeptide-expressing metaplasia (SPEM) are precursors to gastric carcinogenesis. We sought to identify molecular biomarkers of gastric metaplasias and gastric cancer by gene expression profiling of metaplastic lesions from patients. Methods: Complementary DNA microarray analysis was performed on IM and SPEM cells isolated from patient samples using laser capture microdissection. Up-regulated transcripts in metaplastic lesions were confirmed by immunostaining analysis in IM, SPEM, and gastric cancer tissues. Proteins that were highly expressed specifically in gastric cancer tissues were analyzed for their association with survival in a test set (n = 450) and a validation set (n = 502) of samples from gastric cancer patients. Results: Compared with normal chief cells, 858 genes were differentially expressed in IM or SPEM samples. Immunostaining was detected for 12 proteins, including 3 new markers of IM (ACE2, LGALS4, AKR1B10) and 3 of SPEM (OLFM4, LYZ, DPCR1). Of 13 proteins expressed in IM or SPEM, 8 were expressed by 17{\%}-50{\%} of human gastric cancer tissues (MUC13, OLFM4, CDH17, KRT20, MUC5AC, LGALS4, AKR1B10, REG4). Expression of CDH17 or MUC13 correlated with patient survival in the test and validation sets. Multivariate analysis showed that CDH17 was an independent prognostic factor in patients with stage I or node-negative disease. Conclusions: We identified several novel biomarkers for IM, SPEM, and gastric cancer using gene expression profiling of human metaplastic lesions. Expression of CDH17 and MUC13 was up-regulated in gastric cancer tissues. CDH17 is a promising prognostic marker for early stage gastric cancer.",
author = "Lee, {Hyuk Joon} and KiTaek Nam and Park, {Heae Surng} and Kim, {Min A.} and LaFleur, {Bonnie J.} and Hiroyuki Aburatani and Yang, {Han Kwang} and Kim, {Woo Ho} and Goldenring, {James R.}",
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Gene Expression Profiling of Metaplastic Lineages Identifies CDH17 as a Prognostic Marker in Early Stage Gastric Cancer. / Lee, Hyuk Joon; Nam, KiTaek; Park, Heae Surng; Kim, Min A.; LaFleur, Bonnie J.; Aburatani, Hiroyuki; Yang, Han Kwang; Kim, Woo Ho; Goldenring, James R.

In: Gastroenterology, Vol. 139, No. 1, 01.01.2010.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Gene Expression Profiling of Metaplastic Lineages Identifies CDH17 as a Prognostic Marker in Early Stage Gastric Cancer

AU - Lee, Hyuk Joon

AU - Nam, KiTaek

AU - Park, Heae Surng

AU - Kim, Min A.

AU - LaFleur, Bonnie J.

AU - Aburatani, Hiroyuki

AU - Yang, Han Kwang

AU - Kim, Woo Ho

AU - Goldenring, James R.

PY - 2010/1/1

Y1 - 2010/1/1

N2 - Background & Aims: Intestinal metaplasia (IM) and spasmolytic polypeptide-expressing metaplasia (SPEM) are precursors to gastric carcinogenesis. We sought to identify molecular biomarkers of gastric metaplasias and gastric cancer by gene expression profiling of metaplastic lesions from patients. Methods: Complementary DNA microarray analysis was performed on IM and SPEM cells isolated from patient samples using laser capture microdissection. Up-regulated transcripts in metaplastic lesions were confirmed by immunostaining analysis in IM, SPEM, and gastric cancer tissues. Proteins that were highly expressed specifically in gastric cancer tissues were analyzed for their association with survival in a test set (n = 450) and a validation set (n = 502) of samples from gastric cancer patients. Results: Compared with normal chief cells, 858 genes were differentially expressed in IM or SPEM samples. Immunostaining was detected for 12 proteins, including 3 new markers of IM (ACE2, LGALS4, AKR1B10) and 3 of SPEM (OLFM4, LYZ, DPCR1). Of 13 proteins expressed in IM or SPEM, 8 were expressed by 17%-50% of human gastric cancer tissues (MUC13, OLFM4, CDH17, KRT20, MUC5AC, LGALS4, AKR1B10, REG4). Expression of CDH17 or MUC13 correlated with patient survival in the test and validation sets. Multivariate analysis showed that CDH17 was an independent prognostic factor in patients with stage I or node-negative disease. Conclusions: We identified several novel biomarkers for IM, SPEM, and gastric cancer using gene expression profiling of human metaplastic lesions. Expression of CDH17 and MUC13 was up-regulated in gastric cancer tissues. CDH17 is a promising prognostic marker for early stage gastric cancer.

AB - Background & Aims: Intestinal metaplasia (IM) and spasmolytic polypeptide-expressing metaplasia (SPEM) are precursors to gastric carcinogenesis. We sought to identify molecular biomarkers of gastric metaplasias and gastric cancer by gene expression profiling of metaplastic lesions from patients. Methods: Complementary DNA microarray analysis was performed on IM and SPEM cells isolated from patient samples using laser capture microdissection. Up-regulated transcripts in metaplastic lesions were confirmed by immunostaining analysis in IM, SPEM, and gastric cancer tissues. Proteins that were highly expressed specifically in gastric cancer tissues were analyzed for their association with survival in a test set (n = 450) and a validation set (n = 502) of samples from gastric cancer patients. Results: Compared with normal chief cells, 858 genes were differentially expressed in IM or SPEM samples. Immunostaining was detected for 12 proteins, including 3 new markers of IM (ACE2, LGALS4, AKR1B10) and 3 of SPEM (OLFM4, LYZ, DPCR1). Of 13 proteins expressed in IM or SPEM, 8 were expressed by 17%-50% of human gastric cancer tissues (MUC13, OLFM4, CDH17, KRT20, MUC5AC, LGALS4, AKR1B10, REG4). Expression of CDH17 or MUC13 correlated with patient survival in the test and validation sets. Multivariate analysis showed that CDH17 was an independent prognostic factor in patients with stage I or node-negative disease. Conclusions: We identified several novel biomarkers for IM, SPEM, and gastric cancer using gene expression profiling of human metaplastic lesions. Expression of CDH17 and MUC13 was up-regulated in gastric cancer tissues. CDH17 is a promising prognostic marker for early stage gastric cancer.

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