title: Gene expression profiles of thymic neuroendocrine tumors (carcinoids) with ectopic ACTH syndrome reveal novel molecular mechanism.
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 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.
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital Affiliated to Shanghai Jiao-Tong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Yu-fang
authors.initials: YF
authors.lastname: Bi
authors.forename: Rui-xin
authors.initials: RX
authors.lastname: Liu
authors.forename: Lei
authors.initials: L
authors.lastname: Ye
authors.forename: Hai
authors.initials: H
authors.lastname: Fang
authors.forename: Xiao-ying
authors.initials: XY
authors.lastname: Li
authors.forename: Wei-qing
authors.initials: WQ
authors.lastname: Wang
authors.forename: Ji
authors.initials: J
authors.lastname: Zhang
authors.forename: Kan-Kan
authors.initials: KK
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Jiang
authors.forename: Ting-wei
authors.initials: TW
authors.lastname: Su
authors.forename: Zhong-yuan
authors.initials: ZY
authors.lastname: Chen
authors.forename: Guang
authors.initials: G
authors.lastname: Ning
mesh_terms: D000182:ACTH Syndrome, Ectopic / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002276:Carcinoid Tumor / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D018358:Neuroendocrine Tumors / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013950:Thymus Gland / Q000378:metabolism / Q000473:pathology; D013953:Thymus Neoplasms / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger