Gene Expression Changes Accompanying the Duodenal Adenoma-Carcinoma Sequence in Familial Adenomatous Polyposis

Sushrut S. Thiruvengadam, Margaret OʼMalley, Lisa LaGuardia, Rocio Lopez, Zhen Wang, Bonnie L. Shadrach, Yanwen Chen, Chunbiao Li, Martina L. Veigl, Jill S. Barnholtz-Sloan, Rish Pai, James M. Church, Matthew F. Kalady, R. Matthew Walsh, Carol A. Burke

Research output: Contribution to journalArticle

Abstract

OBJECTIVES: Duodenal cancer in familial adenomatous polyposis (FAP) arises from adenomas. Differentially expressed genes (DEGs) in the duodenal adenoma-carcinoma pathway have been identified in murine FAP models, but similar data in patients with FAP are limited. Identifying such changes may have significance in understanding duodenal polyposis therapies and identifying cancer biomarkers. We performed a genome-wide transcriptional analysis to describe the duodenal adenoma-carcinoma sequence and determine changes distinguishing patients with FAP with and without duodenal cancer. METHODS: Transcriptional profiling was performed with the Affymetrix Human Transcriptome Array 2.0 on duodenal biopsies from 12 FAP patients with duodenal cancer (FAP cases) and 12 FAP patients without cancer (FAP controls). DEGs were compared between cancer-normal, adenoma-normal, and cancer-adenoma in FAP cases and between adenomas from FAP cases and FAP controls. Significant results at P < 0.05 were filtered using fold change > 2. RESULTS: Two hundred twenty-four DEGs were identified at an absolute fold change > 2. In adenoma-normal, downregulation of DEGs involved in metabolism of brush border proteins (LCT), lipids (APOB/A4), reactive oxygen species (GSTA2), and retinol (RBP2) was observed. In the cancer-adenoma comparison, upregulation of DEGs involved in cell invasion/migration (POSTN, SPP1) and downregulation of DEGs involved in Paneth differentiation (DEFA5/6) were observed. In the adenoma-adenoma comparison, downregulation of several DEGs (CLCA1, ADH1C, ANXA10) in FAP case adenomas was observed. DEGs with therapeutic potential include SPP1, which is involved in both cyclooxygenase and epidermal growth factor receptor pathways targeted by the sulindac/erlotinib combination for duodenal polyposis. DISCUSSION: We describe DEGs in the human duodenal adenoma-carcinoma sequence in FAP, which may have prognostic and therapeutic significance. Validation studies are needed to confirm these findings.

Original languageEnglish (US)
Pages (from-to)e00053
JournalClinical and translational gastroenterology
Volume10
Issue number6
DOIs
StatePublished - Jun 1 2019

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Adenomatous Polyposis Coli
Adenoma
Carcinoma
Gene Expression
Duodenal Neoplasms
Genes
Down-Regulation
Neoplasms
Sulindac
Validation Studies
Prostaglandin-Endoperoxide Synthases
Tumor Biomarkers
Microvilli
Vitamin A
Transcriptome
Epidermal Growth Factor Receptor
Cell Movement
Reactive Oxygen Species
Up-Regulation

ASJC Scopus subject areas

  • Gastroenterology

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Thiruvengadam, S. S., OʼMalley, M., LaGuardia, L., Lopez, R., Wang, Z., Shadrach, B. L., ... Burke, C. A. (2019). Gene Expression Changes Accompanying the Duodenal Adenoma-Carcinoma Sequence in Familial Adenomatous Polyposis. Clinical and translational gastroenterology, 10(6), e00053. https://doi.org/10.14309/ctg.0000000000000053

Gene Expression Changes Accompanying the Duodenal Adenoma-Carcinoma Sequence in Familial Adenomatous Polyposis. / Thiruvengadam, Sushrut S.; OʼMalley, Margaret; LaGuardia, Lisa; Lopez, Rocio; Wang, Zhen; Shadrach, Bonnie L.; Chen, Yanwen; Li, Chunbiao; Veigl, Martina L.; Barnholtz-Sloan, Jill S.; Pai, Rish; Church, James M.; Kalady, Matthew F.; Walsh, R. Matthew; Burke, Carol A.

In: Clinical and translational gastroenterology, Vol. 10, No. 6, 01.06.2019, p. e00053.

Research output: Contribution to journalArticle

Thiruvengadam, SS, OʼMalley, M, LaGuardia, L, Lopez, R, Wang, Z, Shadrach, BL, Chen, Y, Li, C, Veigl, ML, Barnholtz-Sloan, JS, Pai, R, Church, JM, Kalady, MF, Walsh, RM & Burke, CA 2019, 'Gene Expression Changes Accompanying the Duodenal Adenoma-Carcinoma Sequence in Familial Adenomatous Polyposis', Clinical and translational gastroenterology, vol. 10, no. 6, pp. e00053. https://doi.org/10.14309/ctg.0000000000000053
Thiruvengadam, Sushrut S. ; OʼMalley, Margaret ; LaGuardia, Lisa ; Lopez, Rocio ; Wang, Zhen ; Shadrach, Bonnie L. ; Chen, Yanwen ; Li, Chunbiao ; Veigl, Martina L. ; Barnholtz-Sloan, Jill S. ; Pai, Rish ; Church, James M. ; Kalady, Matthew F. ; Walsh, R. Matthew ; Burke, Carol A. / Gene Expression Changes Accompanying the Duodenal Adenoma-Carcinoma Sequence in Familial Adenomatous Polyposis. In: Clinical and translational gastroenterology. 2019 ; Vol. 10, No. 6. pp. e00053.
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abstract = "OBJECTIVES: Duodenal cancer in familial adenomatous polyposis (FAP) arises from adenomas. Differentially expressed genes (DEGs) in the duodenal adenoma-carcinoma pathway have been identified in murine FAP models, but similar data in patients with FAP are limited. Identifying such changes may have significance in understanding duodenal polyposis therapies and identifying cancer biomarkers. We performed a genome-wide transcriptional analysis to describe the duodenal adenoma-carcinoma sequence and determine changes distinguishing patients with FAP with and without duodenal cancer. METHODS: Transcriptional profiling was performed with the Affymetrix Human Transcriptome Array 2.0 on duodenal biopsies from 12 FAP patients with duodenal cancer (FAP cases) and 12 FAP patients without cancer (FAP controls). DEGs were compared between cancer-normal, adenoma-normal, and cancer-adenoma in FAP cases and between adenomas from FAP cases and FAP controls. Significant results at P < 0.05 were filtered using fold change > 2. RESULTS: Two hundred twenty-four DEGs were identified at an absolute fold change > 2. In adenoma-normal, downregulation of DEGs involved in metabolism of brush border proteins (LCT), lipids (APOB/A4), reactive oxygen species (GSTA2), and retinol (RBP2) was observed. In the cancer-adenoma comparison, upregulation of DEGs involved in cell invasion/migration (POSTN, SPP1) and downregulation of DEGs involved in Paneth differentiation (DEFA5/6) were observed. In the adenoma-adenoma comparison, downregulation of several DEGs (CLCA1, ADH1C, ANXA10) in FAP case adenomas was observed. DEGs with therapeutic potential include SPP1, which is involved in both cyclooxygenase and epidermal growth factor receptor pathways targeted by the sulindac/erlotinib combination for duodenal polyposis. DISCUSSION: We describe DEGs in the human duodenal adenoma-carcinoma sequence in FAP, which may have prognostic and therapeutic significance. Validation studies are needed to confirm these findings.",
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AU - Thiruvengadam, Sushrut S.

AU - OʼMalley, Margaret

AU - LaGuardia, Lisa

AU - Lopez, Rocio

AU - Wang, Zhen

AU - Shadrach, Bonnie L.

AU - Chen, Yanwen

AU - Li, Chunbiao

AU - Veigl, Martina L.

AU - Barnholtz-Sloan, Jill S.

AU - Pai, Rish

AU - Church, James M.

AU - Kalady, Matthew F.

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AU - Burke, Carol A.

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N2 - OBJECTIVES: Duodenal cancer in familial adenomatous polyposis (FAP) arises from adenomas. Differentially expressed genes (DEGs) in the duodenal adenoma-carcinoma pathway have been identified in murine FAP models, but similar data in patients with FAP are limited. Identifying such changes may have significance in understanding duodenal polyposis therapies and identifying cancer biomarkers. We performed a genome-wide transcriptional analysis to describe the duodenal adenoma-carcinoma sequence and determine changes distinguishing patients with FAP with and without duodenal cancer. METHODS: Transcriptional profiling was performed with the Affymetrix Human Transcriptome Array 2.0 on duodenal biopsies from 12 FAP patients with duodenal cancer (FAP cases) and 12 FAP patients without cancer (FAP controls). DEGs were compared between cancer-normal, adenoma-normal, and cancer-adenoma in FAP cases and between adenomas from FAP cases and FAP controls. Significant results at P < 0.05 were filtered using fold change > 2. RESULTS: Two hundred twenty-four DEGs were identified at an absolute fold change > 2. In adenoma-normal, downregulation of DEGs involved in metabolism of brush border proteins (LCT), lipids (APOB/A4), reactive oxygen species (GSTA2), and retinol (RBP2) was observed. In the cancer-adenoma comparison, upregulation of DEGs involved in cell invasion/migration (POSTN, SPP1) and downregulation of DEGs involved in Paneth differentiation (DEFA5/6) were observed. In the adenoma-adenoma comparison, downregulation of several DEGs (CLCA1, ADH1C, ANXA10) in FAP case adenomas was observed. DEGs with therapeutic potential include SPP1, which is involved in both cyclooxygenase and epidermal growth factor receptor pathways targeted by the sulindac/erlotinib combination for duodenal polyposis. DISCUSSION: We describe DEGs in the human duodenal adenoma-carcinoma sequence in FAP, which may have prognostic and therapeutic significance. Validation studies are needed to confirm these findings.

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