Gene expression profiles of thymic neuroendocrine tumors (carcinoids) with ectopic ACTH syndrome reveal novel molecular mechanism

Yu-fang Bi, Rui-xin Liu, Lei Ye, Hai Fang, Xiao-ying Li, Wei-qing Wang, Ji Zhang, Kan-Kan Wang, Lei Jiang, Ting-wei Su, Zhong-yuan Chen, Guang Ning

Research output: Contribution to journalArticle (Academic Journal)peer-review

11 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)1273-82
Number of pages10
JournalEndocrine-Related Cancer
Volume16
Issue number4
DOIs
Publication statusPublished - Dec 2009

Keywords

  • Oligonucleotide Array Sequence Analysis
  • Humans
  • Reverse Transcriptase Polymerase Chain Reaction
  • Neuroendocrine Tumors
  • RNA, Messenger
  • Gene Expression Profiling
  • Thymus Gland
  • Adult
  • Thymus Neoplasms
  • Carcinoid Tumor
  • Tumor Markers, Biological
  • Female
  • Male
  • Signal Transduction
  • ACTH Syndrome, Ectopic

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