Novel markers for enterochromaffin cells and gastrointestinal neuroendocrine carcinomas

Justyna Leja, Ahmed Essaghir, Magnus Essand, Kenneth Wester, Kjell Öberg, Thomas H. Tötterman, Ricardo Lloyd, George Vasmatzis, Jean Baptiste Demoulin, Valeria Giandomenico

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)261-272
Number of pages12
JournalModern Pathology
Volume22
Issue number2
DOIs
StatePublished - Feb 2009

Fingerprint

Enterochromaffin Cells
Neuroendocrine Carcinoma
Neuroendocrine Cells
Genes
Neoplasm Metastasis
CCR10 Receptors
Biomarkers
Odorant Receptors
Laser Capture Microdissection
Serpins
Ionotropic Glutamate Receptors
CXC Chemokines
Neoplasms
Microdissection
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Liver
antineoplaston A10
Jejunum
G-Protein-Coupled Receptors
Computational Biology

Keywords

  • Bioinformatics analysis
  • Gastrointestinal neuroendocrine carcinoma
  • Novel markers

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Leja, J., Essaghir, A., Essand, M., Wester, K., Öberg, K., Tötterman, T. H., ... Giandomenico, V. (2009). Novel markers for enterochromaffin cells and gastrointestinal neuroendocrine carcinomas. Modern Pathology, 22(2), 261-272. https://doi.org/10.1038/modpathol.2008.174

Novel markers for enterochromaffin cells and gastrointestinal neuroendocrine carcinomas. / Leja, Justyna; Essaghir, Ahmed; Essand, Magnus; Wester, Kenneth; Öberg, Kjell; Tötterman, Thomas H.; Lloyd, Ricardo; Vasmatzis, George; Demoulin, Jean Baptiste; Giandomenico, Valeria.

In: Modern Pathology, Vol. 22, No. 2, 02.2009, p. 261-272.

Research output: Contribution to journalArticle

Leja, J, Essaghir, A, Essand, M, Wester, K, Öberg, K, Tötterman, TH, Lloyd, R, Vasmatzis, G, Demoulin, JB & Giandomenico, V 2009, 'Novel markers for enterochromaffin cells and gastrointestinal neuroendocrine carcinomas', Modern Pathology, vol. 22, no. 2, pp. 261-272. https://doi.org/10.1038/modpathol.2008.174
Leja J, Essaghir A, Essand M, Wester K, Öberg K, Tötterman TH et al. Novel markers for enterochromaffin cells and gastrointestinal neuroendocrine carcinomas. Modern Pathology. 2009 Feb;22(2):261-272. https://doi.org/10.1038/modpathol.2008.174
Leja, Justyna ; Essaghir, Ahmed ; Essand, Magnus ; Wester, Kenneth ; Öberg, Kjell ; Tötterman, Thomas H. ; Lloyd, Ricardo ; Vasmatzis, George ; Demoulin, Jean Baptiste ; Giandomenico, Valeria. / Novel markers for enterochromaffin cells and gastrointestinal neuroendocrine carcinomas. In: Modern Pathology. 2009 ; Vol. 22, No. 2. pp. 261-272.
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