Global Expression Analysis of Well-Differentiated Pancreatic Endocrine Neoplasms Using Oligonucleotide Microarrays

Anirban Maitra, Donna E. Hansel, Pedram Argani, Raheela Ashfaq, Ayman Rahman, Ali Naji, Shaoping Deng, Joseph Geradts, Lesley Ann Hawthorne, Michael House, Charles J. Yeo

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

Purpose: Pancreatic endocrine neoplasms (PENs) are rare, mostly well-differentiated endocrine neoplasms, whose biology has been poorly characterized. Global expression microarrays can document abnormal pathways that impact on tumorigenesis and disease progression. Experimental Design: RNA was extracted from eight well-differentiated PENs and three highly enriched pancreatic islet cell samples (80-90% purity), and examined using the Affymetrix U133A oligonucleotide microarray. Microarray data were normalized using dCHIP (www.dCHIP.org) for identification of differentially expressed genes. PEN tissue microarrays were constructed from 53 archival PENs for immunohistochemical validation of microarray data. Results: Sixty-six transcripts were overexpressed ≥3-fold in PENs compared with normal islet cells, including putative oncogenes (MLLT10/AF10), growth factors [insulin-like growth factor-binding protein 3 (IGFBP3)], cell adhesion and migration molecules (fibronectin), and endothelial elements (MUC18/MelCAM and CD31). A total of 119 transcripts were underexpressed ≤3-fold in PENs compared with normal islet cells, including cell cycle checkpoint proteins (p21/Cip1), the MIC2 (CD99) cell surface glycoprotein, putative metastasis suppressor genes (NME3), and junD, a MEN1-regulated transcription factor. Using PEN tissue microarrays, we confirmed the differential up-regulation of IGFBP3 (70%) and fibronectin (22%) and differential down-regulation of p21 (46%) and MIC2 (CD99; 91%) in PENs versus normal pancreatic islets. IGFBP3 overexpression was significantly more common in metastatic (93%) versus primary PEN lesions (60%), P = 0.022. Fibronectin overexpression demonstrated a trend toward significance in lymphatic PEN metastases (55%) compared with primary PEN lesions (24%; P = 0.14). Conclusions: Global expression analysis provides insight into tumorigenic pathways in PENs and may identify potential prognostic and therapeutic markers for these uncommon neoplasms.

Original languageEnglish (US)
Pages (from-to)5988-5995
Number of pages8
JournalClinical Cancer Research
Volume9
Issue number16 I
StatePublished - Dec 1 2003
Externally publishedYes

Fingerprint

Oligonucleotide Array Sequence Analysis
Pancreatic Neoplasms
Islets of Langerhans
Insulin-Like Growth Factor Binding Protein 3
Fibronectins
Multiple Endocrine Neoplasia Type 1
Cell Cycle Proteins
Membrane Glycoproteins
Cell Adhesion Molecules
Cell Cycle Checkpoints
Tumor Suppressor Genes
Oncogenes
Cell Movement
Disease Progression
Neoplasms
Intercellular Signaling Peptides and Proteins
Carcinogenesis
Research Design
Transcription Factors
Up-Regulation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Maitra, A., Hansel, D. E., Argani, P., Ashfaq, R., Rahman, A., Naji, A., ... Yeo, C. J. (2003). Global Expression Analysis of Well-Differentiated Pancreatic Endocrine Neoplasms Using Oligonucleotide Microarrays. Clinical Cancer Research, 9(16 I), 5988-5995.

Global Expression Analysis of Well-Differentiated Pancreatic Endocrine Neoplasms Using Oligonucleotide Microarrays. / Maitra, Anirban; Hansel, Donna E.; Argani, Pedram; Ashfaq, Raheela; Rahman, Ayman; Naji, Ali; Deng, Shaoping; Geradts, Joseph; Hawthorne, Lesley Ann; House, Michael; Yeo, Charles J.

In: Clinical Cancer Research, Vol. 9, No. 16 I, 01.12.2003, p. 5988-5995.

Research output: Contribution to journalArticle

Maitra, A, Hansel, DE, Argani, P, Ashfaq, R, Rahman, A, Naji, A, Deng, S, Geradts, J, Hawthorne, LA, House, M & Yeo, CJ 2003, 'Global Expression Analysis of Well-Differentiated Pancreatic Endocrine Neoplasms Using Oligonucleotide Microarrays', Clinical Cancer Research, vol. 9, no. 16 I, pp. 5988-5995.
Maitra A, Hansel DE, Argani P, Ashfaq R, Rahman A, Naji A et al. Global Expression Analysis of Well-Differentiated Pancreatic Endocrine Neoplasms Using Oligonucleotide Microarrays. Clinical Cancer Research. 2003 Dec 1;9(16 I):5988-5995.
Maitra, Anirban ; Hansel, Donna E. ; Argani, Pedram ; Ashfaq, Raheela ; Rahman, Ayman ; Naji, Ali ; Deng, Shaoping ; Geradts, Joseph ; Hawthorne, Lesley Ann ; House, Michael ; Yeo, Charles J. / Global Expression Analysis of Well-Differentiated Pancreatic Endocrine Neoplasms Using Oligonucleotide Microarrays. In: Clinical Cancer Research. 2003 ; Vol. 9, No. 16 I. pp. 5988-5995.
@article{80722d00087d435888c29882b5f1ddf2,
title = "Global Expression Analysis of Well-Differentiated Pancreatic Endocrine Neoplasms Using Oligonucleotide Microarrays",
abstract = "Purpose: Pancreatic endocrine neoplasms (PENs) are rare, mostly well-differentiated endocrine neoplasms, whose biology has been poorly characterized. Global expression microarrays can document abnormal pathways that impact on tumorigenesis and disease progression. Experimental Design: RNA was extracted from eight well-differentiated PENs and three highly enriched pancreatic islet cell samples (80-90{\%} purity), and examined using the Affymetrix U133A oligonucleotide microarray. Microarray data were normalized using dCHIP (www.dCHIP.org) for identification of differentially expressed genes. PEN tissue microarrays were constructed from 53 archival PENs for immunohistochemical validation of microarray data. Results: Sixty-six transcripts were overexpressed ≥3-fold in PENs compared with normal islet cells, including putative oncogenes (MLLT10/AF10), growth factors [insulin-like growth factor-binding protein 3 (IGFBP3)], cell adhesion and migration molecules (fibronectin), and endothelial elements (MUC18/MelCAM and CD31). A total of 119 transcripts were underexpressed ≤3-fold in PENs compared with normal islet cells, including cell cycle checkpoint proteins (p21/Cip1), the MIC2 (CD99) cell surface glycoprotein, putative metastasis suppressor genes (NME3), and junD, a MEN1-regulated transcription factor. Using PEN tissue microarrays, we confirmed the differential up-regulation of IGFBP3 (70{\%}) and fibronectin (22{\%}) and differential down-regulation of p21 (46{\%}) and MIC2 (CD99; 91{\%}) in PENs versus normal pancreatic islets. IGFBP3 overexpression was significantly more common in metastatic (93{\%}) versus primary PEN lesions (60{\%}), P = 0.022. Fibronectin overexpression demonstrated a trend toward significance in lymphatic PEN metastases (55{\%}) compared with primary PEN lesions (24{\%}; P = 0.14). Conclusions: Global expression analysis provides insight into tumorigenic pathways in PENs and may identify potential prognostic and therapeutic markers for these uncommon neoplasms.",
author = "Anirban Maitra and Hansel, {Donna E.} and Pedram Argani and Raheela Ashfaq and Ayman Rahman and Ali Naji and Shaoping Deng and Joseph Geradts and Hawthorne, {Lesley Ann} and Michael House and Yeo, {Charles J.}",
year = "2003",
month = "12",
day = "1",
language = "English (US)",
volume = "9",
pages = "5988--5995",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "16 I",

}

TY - JOUR

T1 - Global Expression Analysis of Well-Differentiated Pancreatic Endocrine Neoplasms Using Oligonucleotide Microarrays

AU - Maitra, Anirban

AU - Hansel, Donna E.

AU - Argani, Pedram

AU - Ashfaq, Raheela

AU - Rahman, Ayman

AU - Naji, Ali

AU - Deng, Shaoping

AU - Geradts, Joseph

AU - Hawthorne, Lesley Ann

AU - House, Michael

AU - Yeo, Charles J.

PY - 2003/12/1

Y1 - 2003/12/1

N2 - Purpose: Pancreatic endocrine neoplasms (PENs) are rare, mostly well-differentiated endocrine neoplasms, whose biology has been poorly characterized. Global expression microarrays can document abnormal pathways that impact on tumorigenesis and disease progression. Experimental Design: RNA was extracted from eight well-differentiated PENs and three highly enriched pancreatic islet cell samples (80-90% purity), and examined using the Affymetrix U133A oligonucleotide microarray. Microarray data were normalized using dCHIP (www.dCHIP.org) for identification of differentially expressed genes. PEN tissue microarrays were constructed from 53 archival PENs for immunohistochemical validation of microarray data. Results: Sixty-six transcripts were overexpressed ≥3-fold in PENs compared with normal islet cells, including putative oncogenes (MLLT10/AF10), growth factors [insulin-like growth factor-binding protein 3 (IGFBP3)], cell adhesion and migration molecules (fibronectin), and endothelial elements (MUC18/MelCAM and CD31). A total of 119 transcripts were underexpressed ≤3-fold in PENs compared with normal islet cells, including cell cycle checkpoint proteins (p21/Cip1), the MIC2 (CD99) cell surface glycoprotein, putative metastasis suppressor genes (NME3), and junD, a MEN1-regulated transcription factor. Using PEN tissue microarrays, we confirmed the differential up-regulation of IGFBP3 (70%) and fibronectin (22%) and differential down-regulation of p21 (46%) and MIC2 (CD99; 91%) in PENs versus normal pancreatic islets. IGFBP3 overexpression was significantly more common in metastatic (93%) versus primary PEN lesions (60%), P = 0.022. Fibronectin overexpression demonstrated a trend toward significance in lymphatic PEN metastases (55%) compared with primary PEN lesions (24%; P = 0.14). Conclusions: Global expression analysis provides insight into tumorigenic pathways in PENs and may identify potential prognostic and therapeutic markers for these uncommon neoplasms.

AB - Purpose: Pancreatic endocrine neoplasms (PENs) are rare, mostly well-differentiated endocrine neoplasms, whose biology has been poorly characterized. Global expression microarrays can document abnormal pathways that impact on tumorigenesis and disease progression. Experimental Design: RNA was extracted from eight well-differentiated PENs and three highly enriched pancreatic islet cell samples (80-90% purity), and examined using the Affymetrix U133A oligonucleotide microarray. Microarray data were normalized using dCHIP (www.dCHIP.org) for identification of differentially expressed genes. PEN tissue microarrays were constructed from 53 archival PENs for immunohistochemical validation of microarray data. Results: Sixty-six transcripts were overexpressed ≥3-fold in PENs compared with normal islet cells, including putative oncogenes (MLLT10/AF10), growth factors [insulin-like growth factor-binding protein 3 (IGFBP3)], cell adhesion and migration molecules (fibronectin), and endothelial elements (MUC18/MelCAM and CD31). A total of 119 transcripts were underexpressed ≤3-fold in PENs compared with normal islet cells, including cell cycle checkpoint proteins (p21/Cip1), the MIC2 (CD99) cell surface glycoprotein, putative metastasis suppressor genes (NME3), and junD, a MEN1-regulated transcription factor. Using PEN tissue microarrays, we confirmed the differential up-regulation of IGFBP3 (70%) and fibronectin (22%) and differential down-regulation of p21 (46%) and MIC2 (CD99; 91%) in PENs versus normal pancreatic islets. IGFBP3 overexpression was significantly more common in metastatic (93%) versus primary PEN lesions (60%), P = 0.022. Fibronectin overexpression demonstrated a trend toward significance in lymphatic PEN metastases (55%) compared with primary PEN lesions (24%; P = 0.14). Conclusions: Global expression analysis provides insight into tumorigenic pathways in PENs and may identify potential prognostic and therapeutic markers for these uncommon neoplasms.

UR - http://www.scopus.com/inward/record.url?scp=0347364774&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0347364774&partnerID=8YFLogxK

M3 - Article

C2 - 14676124

AN - SCOPUS:0347364774

VL - 9

SP - 5988

EP - 5995

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 16 I

ER -