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Y Bi, Endocrinology, Ruijin Hospital, Shanghai, China
R Liu, Endocrinology, Rujin Hospital, Shanghai, China
L Ye, endocrinology, Ruijin Hospital, Shanghai, 200025, China
H Fang, State Key Laboratory of Medical Genomics, Shanghai, China
X Li, Endocrinology, RuiJin Hospital, Shanghai, China
W Wang, Endocrinology, Ruijin Hospital, Shanghai, China
J Zhang, Shanghai, China
K Wang, Shanghai, China
L Jiang, Endocrinology, Ruijin Hospital, Shanghai, China
T Su, Endocrinology, Ruijin hospital, Shanghai, China
Z Chen, Thoracic Surgery, Ruijin Hospital, Shanghai, China
G Ning, Endocrinology, Ruijin Hospital, Shanghai, China

Correspondence: Lei Ye, Email: feifeiyelei{at}hotmail.com

Abstract

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 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 normal thymus. Totally 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 Notch signaling pathway was likely underlying the neuroendocrine features of this type of tumors. Moreover, the inhibition of the immunity and the 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 distinguished 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 neuroendocrine tumor. This study hence has provided not only a detailed comprehension of the molecular pathogenesis of thymic carcinoid with ectopic ACTH syndrome, but also a road map to approach thymic neuroendocrine tumors at the system level.