TY - JOUR
T1 - Gene expression changes accompanying the duodenal adenoma-carcinoma sequence in familial adenomatous polyposis
AU - Thiruvengadam, Sushrut S.
AU - O’Malley, 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 K.
AU - Church, James M.
AU - Kalady, Matthew F.
AU - Matthew Walsh, R.
AU - Burke, Carol A.
N1 - Funding Information:
Guarantor of the article: Sushrut S. Thiruvengadam, MD. Specific author contributions: Study concept and design: S.S.T. and C.A.B. Acquisition of data (retrospective identification and selection of patients): S.S.T., R.L., M.O. and L.L. Acquisition of data (identification and preparation of archived tissue samples for transcriptional profiling): S.S.T. and R.K.P. Acquisition of data (transcriptional profiling): M.L.V. and C.L. Acquisition of data (PCR verification): S.S.T., Z.W., and B.S. Analysis and interpretation of the data: S.S.T., R.L., Y.C., J.S.B., and C.A.B. Drafting of the manuscript: S.S.T. Critical revision of the manuscript for important intellectual content: C.A.B., J.B.S., M.L.V., B.S., and Z.W. All authors have reviewed the final submitted draft. Financial support: Grant support provided by Cleveland Clinic Research Program Committees Award (RPC 2014–1047). Technical support for this work was provided by the Gene Expression and Genotyping Facility, a component of the Integrated Genomic Shared Resource sponsored by the Case Comprehensive Cancer Center (P30 CA43703). This work was independent of this funding. Potential competing interests: C.A.B. reports the following relevant financial disclosures: grants from Cancer Prevention Pharmaceuticals, Ferring Pharmaceuticals, consultant royalties and personal fees from Sucampo, Aries, and Salix Pharmaceuticals. M.K. reports the following relevant financial disclosures: consulting honorarium from Helomics and TransEnterix. The other authors affirm that they have no relevant financial or personal conflicts to disclose.
Publisher Copyright:
© 2019 The Author(s).
PY - 2019/6/1
Y1 - 2019/6/1
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 canceradenoma 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 adenomaadenoma 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.
AB - 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 canceradenoma 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 adenomaadenoma 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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U2 - 10.14309/ctg.0000000000000053
DO - 10.14309/ctg.0000000000000053
M3 - Article
C2 - 31211760
AN - SCOPUS:85069234519
SN - 2155-384X
VL - 10
JO - Clinical and translational gastroenterology
JF - Clinical and translational gastroenterology
IS - 6
M1 - e-00053
ER -