TY - JOUR
T1 - Novel markers for enterochromaffin cells and gastrointestinal neuroendocrine carcinomas
AU - Leja, Justyna
AU - Essaghir, Ahmed
AU - Essand, Magnus
AU - Wester, Kenneth
AU - Öberg, Kjell
AU - Tötterman, Thomas H.
AU - Lloyd, Ricardo
AU - Vasmatzis, George
AU - Demoulin, Jean Baptiste
AU - Giandomenico, Valeria
N1 - Funding Information:
We thank Professor Emeritus Lars Grimelius, Dr Janet L Cunningham, Professor Per-Uno Malmström, Assistant Professor Manuel de la Torre and Assistant Professor Alkwin Wanders, Uppsala University Hospital for assistance with pathological examinations of samples and surgical material. We also thank Åsa Forsberg, Ulrika Larsson, Simin Tahma- sebpoor, Ulrika Johansson, Marcus Runeson, Eva Wahlund and Dr Jan Gravé for excellent technical assistance. AE and JBD were supported by grants from the Région Wallonne and from the Fonds pour la Recherche Scientifique (FNRS), Belgium. The Verto Institute, Dr Raymond and Beverly Sackler and Tore Nilsson’s Foundation supported this work.
PY - 2009/2
Y1 - 2009/2
N2 - The gene expression profile of metastasizing serotonin-producing neuroendocrine carcinomas, which arise from enterochromaffin cells in the jejunum and ileum, is still largely unknown. The aim of this study was to identify genes and proteins, which are preferentially expressed by neuroendocrine carcinoma and enterochromaffin cells and therefore potential novel biomarkers and/or therapeutic targets. Six carcinoma specimens and six normal ileal mucosas were profiled by Affymetrix microarrays. Advanced bioinformatics identified differentially and specifically expressed genes, which were validated by quantitative real-time-PCR on tumor cells extracted by laser capture microdissection and normal enterochromaffin cells extracted by immunolaser capture microdissection. We identified six novel marker genes for neuroendocrine carcinoma cells: paraneoplastic antigen Ma2 (PNMA2), testican-1 precursor (SPOCK1), serpin A10 (SERPINA10), glutamate receptor ionotropic AMPA 2 (GRIA2), G protein-coupled receptor 112 (GPR112) and olfactory receptor family 51 subfamily E member 1 (OR51E1). GRIA2 is specifically expressed by neuroendocrine carcinoma cells whereas the others are also expressed by normal enterochromaffin cells. GPR112 and OR51E1 encode proteins associated with the plasma membrane and may therefore become targets for antibody-based diagnosis and therapy. Hierarchical clustering shows high similarity between primary lesions and liver metastases. However, chemokine C-X-C motif ligand 14 (CXCL14) and NK2 transcription factor related locus 3 Drosophila (NKX2-3) are expressed to a lower level in liver metastases than in primary tumors and normal enterochromaffin cells, which implies a role in neuroendocrine carcinoma differentiation. In conclusion, this study provides a list of genes, which possess relatively specific expression to enterochromaffin and neuroendocrine carcinoma cells and genes with differential expression between primary tumors and metastases. We verified six novel marker genes that may be developed as biomarkers and/or therapeutic targets.
AB - The gene expression profile of metastasizing serotonin-producing neuroendocrine carcinomas, which arise from enterochromaffin cells in the jejunum and ileum, is still largely unknown. The aim of this study was to identify genes and proteins, which are preferentially expressed by neuroendocrine carcinoma and enterochromaffin cells and therefore potential novel biomarkers and/or therapeutic targets. Six carcinoma specimens and six normal ileal mucosas were profiled by Affymetrix microarrays. Advanced bioinformatics identified differentially and specifically expressed genes, which were validated by quantitative real-time-PCR on tumor cells extracted by laser capture microdissection and normal enterochromaffin cells extracted by immunolaser capture microdissection. We identified six novel marker genes for neuroendocrine carcinoma cells: paraneoplastic antigen Ma2 (PNMA2), testican-1 precursor (SPOCK1), serpin A10 (SERPINA10), glutamate receptor ionotropic AMPA 2 (GRIA2), G protein-coupled receptor 112 (GPR112) and olfactory receptor family 51 subfamily E member 1 (OR51E1). GRIA2 is specifically expressed by neuroendocrine carcinoma cells whereas the others are also expressed by normal enterochromaffin cells. GPR112 and OR51E1 encode proteins associated with the plasma membrane and may therefore become targets for antibody-based diagnosis and therapy. Hierarchical clustering shows high similarity between primary lesions and liver metastases. However, chemokine C-X-C motif ligand 14 (CXCL14) and NK2 transcription factor related locus 3 Drosophila (NKX2-3) are expressed to a lower level in liver metastases than in primary tumors and normal enterochromaffin cells, which implies a role in neuroendocrine carcinoma differentiation. In conclusion, this study provides a list of genes, which possess relatively specific expression to enterochromaffin and neuroendocrine carcinoma cells and genes with differential expression between primary tumors and metastases. We verified six novel marker genes that may be developed as biomarkers and/or therapeutic targets.
KW - Bioinformatics analysis
KW - Gastrointestinal neuroendocrine carcinoma
KW - Novel markers
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U2 - 10.1038/modpathol.2008.174
DO - 10.1038/modpathol.2008.174
M3 - Article
C2 - 18953328
AN - SCOPUS:59149090670
SN - 0893-3952
VL - 22
SP - 261
EP - 272
JO - Modern Pathology
JF - Modern Pathology
IS - 2
ER -