Although there has been increased knowledge about the molecular biology of
neuroendocrine tumors (NETs), little is known about thymic
carcinoids and even less about those with excessive
hormone disorders, such as
ectopic ACTH syndrome. This study was designed to gain insights into the molecular networks underlying the
tumorigenesis of thymic
carcinoids with
ACTH secretion. By an approach integrating
cDNA microarray and methods of computational biology, we compare gene expression profile between
ACTH-producing thymic
carcinoids and the normal thymus. In total, there are 63
biological categories increased and 108 decreased in thymic
carcinoids. Cell proliferation was stimulated, which may explain the relatively uncontrolled cell growth of the
tumor. Dysregulation of the Notch-signaling pathway was likely to be underlying the neuroendocrine features of this type of
tumors. Moreover, inhibition of immunity and increased
neuropeptide signaling molecules (
POMC and its sorting molecule CPE) made the clinical manifestation reasonable and thus validated the array data. In conclusion, thymic
carcinoids have a distinct gene expression pattern from the normal thymus, and they are characterized by deregulations of a series of biofunctions, which may be involved in the development of NETs. Hence, this study has provided not only a detailed comprehension of the molecular pathogenesis of thymic
carcinoids with
ectopic ACTH syndrome, but also a road map to approach thymic NETs at the system level.