Proteogenomic profiling of thymic and pulmonary neuroendocrine neoplasia.
Ontology highlight
ABSTRACT: This study represents a proteogenomic resource for thymic and pulmonary neuroendocrine neoplasia (NEN) and provides a proteomgenomic diagnostic signature for classification of low and high grade NEN.
Project description:Gastroentero-pancreatic neuroendocrine neoplasm(GEP-NEN) is consisted of neuroendocrine tumor and neuroendocrine carcinoma, which is a lethal, but under-investigated disease owing to its rarity. We established an organoid library of GEP-NEN and added their comprehensive molecular characterization.
Project description: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. Transcriptome profilings were performed to identify differentially expressed cDNAs between five samples (NCs) from thymic tumor-suffering patients with ectopic ACTH syndrome (i.e., NC1, NC2, NC3, NC4, NC5, NC6) and six samples (ACs) of the noncancerous thymuses (i.e., AC1, AC2, AC3, AC4, AC5).
Project description: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.
Project description:Neuroendocrine neoplasms of the gallbladder and liver occur rarely in dogs and humans. A recent reclassification of human neuroendocrine neoplasms by the World Health Organization has refined categorization of these tumors by morphology, replicative indices, and molecular signatures. In humans, these factors correlate with survival outcomes. Improved characterization of these tumors is needed in dogs to identify diagnostic biomarkers and determine therapeutic strategies. To achieve this objective, the proteome of 3 canine hepatobiliary neoplasms was compared to normal canine adrenal and liver tissue from formalin-fixed paraffin-embedded samples. Thirty-two upregulated and 121 downregulated differentially expressed proteins were identified in the hepatobiliary neuroendocrine neoplasm samples. Among the upregulated proteins is galectin-1, a multivalent carbohydrate binding protein known to play a role in lung and pancreatic neuroendocrine neoplasia development and progression in humans. Drugs targeting the galectin family have shown promise as anticancer therapeutics in cervical cancer, prostate cancer, lung and pancreatic neuroendocrine neoplasia in human medicine. Galectin-1 may represent a novel treatment target in hepatobiliary neuroendocrine neoplasia in both humans and dogs.
Project description:The RNA isolated from 60 Neuroendocrine Neoplasm (NEN) was analysed to identify differentially expressed transcripts and fusion transcripts. Library preparation was performed using two different kit: TruSeq Stranded Total RNA (Illumina) for frozen samples and extracted RNAs, and TruSeq RNA Exome (Illumina) for FFPE samples.
Project description:The DNA isolated from 44 either frozen or FFPE Neuroendocrine Neoplasm (NEN) was analysed by NGS, to identify genes more likely to be subject to sequence variations among 523 cancer-related ones.
Project description:To characterize pancreatic neuroendocrine tumor at protein level, we performed mass spectromery-based proteome analysis using clinical FFPE tissue samples.