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.