TERT Expression and Clinical Outcome in Pulmonary Carcinoids
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE261443 | GEO | 2024/12/21
REPOSITORIES: GEO
Similar Datasets
Project description:TERT Expression and Clinical Outcome in Pulmonary Carcinoids
| PRJNA1086956 | ENA
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.
2009-08-13 | GSE17619 | GEO
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).
2009-08-13 | E-GEOD-17619 | biostudies-arrayexpress
Project description:Analysis of genetic alterations within pulmonary carcinoids by array comparative genomic hybridization
2011-06-01 | E-MEXP-3145 | biostudies-arrayexpress
Project description:The goal of this study was to characterize and classify pulmonary neuroendocrine tumors based on Array Comparative Genomic Hybridization (aCGH). Using aCGH, we performed karyotype analysis of 33 small cell lung cancer (SCLC) tumors, 13 SCLC cell lines, 19 bronchial carcinoids, and 9 gastrointestinal (GI) carcinoids. In contrast to the relatively stable karyotypes of carcinoid tumors, the karyotypes of SCLC tumors and cell lines were highly aberrant. High copy number (CN) gains were detected in SCLC tumors and cell lines in cytogenetic bands encoding JAK2, FGFR1, and MYC family members. In some of those samples, the CN of these genes exceeded 100, suggesting that they could represent driver alterations and potential drug targets in subgroups of SCLC patients. Recurrent CN alterations of a total of 203 genes, including the RB1 gene, and 59 microRNAs, most of which locate in the DLK1-DIO3 domain, were observed in SCLC tumors, bronchial carcinoids and carcinoids of GI origin; in contrast, CN alterations of the TP53 gene and the MYC family members were observed more frequently in SCLC. These findings suggest the existence of partially shared tumor-specific CN alterations in these tumors. Furthermore, we demonstrated that the aCGH profile of SCLC cell lines highly resemble that of clinical SCLC specimens. Finally, by analyzing potential drug targets, we provide a genomics based rationale for targeting the AKT-mTOR and apoptosis pathways in SCLC. Carcinoids, including 19 bronchial carcinoids and 9 carcinoid of gastrointestinal origin, and small cell lung cancer, including 33 patients' tumor samples and 13 cell line samples, were compared.
2010-04-22 | E-GEOD-21468 | biostudies-arrayexpress
Project description:Background: It is still uncertain whether carcinoids of the lung and gastrointestinal (GI) tract have a common origin or whether they are closer in origin to carcinomas of the same organs. MicroRNA (miRNA) expression may clarify their nature and origin. Methods: First, to verify whether formalin-fixed paraffin-embedded (FFPE) samples retain the expression signature of the tissue, miRNA expression was compared between FFPE and frozen samples. Second, we selected surgically resected FFPE samples of pulmonary and GI carcinoids, as well as other types of tumors and normal tissues from each organ, and we compared the comprehensive expression patterns of miRNAs by microarray. These data were analyzed by hierarchical clustering and consensus clustering with non-negative matrix factorization (NMF). Results: The miRNA expression profiles of FFPE and frozen samples correlated quite well. In the first hierarchical clustering, most of the carcinoids formed one major cluster with loose subpartitioning into each organ type, while the second major cluster mainly comprised adenocarcinomas and normal tissues. The NMF approach largely supported hierarchical clustering. In the additional cluster analysis comparing carcinoids to small-cell lung carcinomas (SCLCs), carcinoids formed a distinct cluster, while SCLCs grouped together with pulmonary adenocarcinomas and normal lung tissues in another major cluster. Furthermore, we found some miRNAs that exhibited significant expression in carcinoids. Conclusion: Carcinoids had a characteristic pattern of miRNA expression, suggesting a common origin for pulmonary and GI carcinoids. The expression profiles were different in carcinoids and SCLCs, indicating distinct histogenesis of these neuroendocrine tumors.
2016-02-01 | GSE77380 | GEO
Project description:Background/aims: Lung carcinoids are uncommon neuroendocrine tumours. Molecular features of lung carcinoids have been poorly defined. microRNAs (miRNAs) are potent gene expression regulators with important roles in cancer development and progression. However, little is known on the role of miRNAs in the pathogenesis of lung carcinoids. Our goals were to identify commonly deregulated miRNAs in a rare case of lung carcinoid of typical histology with metastasis, as well as map miRNA target genes in pathways potentially associated with disease development and progression. Methods: miRNA expression profiles were assessed using the TaqMan Low Density Arrays, which is a platform including 384 miRNAs. miRNA profiles were generated in the tumor and its corresponding lymph node metastasis, compared to reference normal lung tissues. Furthermore, miRNA expression was validated in a separate, publicly available external dataset (n=19 typical lung carcinoids; 2/19 were metastatic tumors, compared to six normal lung tissues, GSE77380). Following this analysis, computational tools were applied for data interpretation. miRTarBase was used to determine miRNA-target genes, followed by ToppGene Suite analysis to identify pathways and biological functions. In addition, the expression of genes targeted by miRNAs was validated in a second, separate external dataset (n=13 tumour samples, GSE35679). GEO2R data analysis tool was used in both validation analyses (miRNAs and genes). Results: We identified 15 commonly significantly downregulated miRNAs (fold change, FC≥2 and p<0.05) in the tumour and its paired metastasis, with further decreasing levels in the metastatic lesion. Downregulation of miR-126-3p and miR-146b-5p was validated in the external dataset GSE77380. In addition, SOX2 and TCF4 genes, targeted by miR-126-3p, were consistently overexpressed in a subset of six typical lung carcinoids from the external dataset GSE35679. Pathways analysis showed that miRNAs miR-126-3p and miR-146b-5p target genes with a role in the regulation of adaptive immune response. Conclusion: Our results contribute to the identification of miRNA expression changes in a typical lung carcinoid and its corresponding lymph node metastasis. Down-regulated levels of miR-126-3p and miR-146b-5p and target gene over-expression could play a role in the progression of this case of primary typical lung carcinoid to regional metastasis. Identified miRNAs and target genes are potential candidates for validation in a larger number of cases.
2022-10-10 | GSE138708 | GEO
Project description:High-resoution array comparative genomic hybridization of pulmonary carcinoids with a favorable and a poor disease outcome. Data set from a complementary experiment looking for differentially expressed genes is also deposited at ArrayExpress under accession ID E-MEXP-3790 (http://www.ebi.ac.uk/arrayexpress/experiments/E-MEXP-3790).
2013-06-21 | E-MEXP-3806 | biostudies-arrayexpress
Project description:Lung carcinoids (LCs) are rare and slow growing primary lung neoplasms that are understudied. Here, we performed targeted exome sequencing using a 354-cancer gene panel (n=29), mRNA sequencing (n=30) and DNA methylation assay (n=18) on macro-dissected lung carcinoids. The mutations we identified were enriched for genes involved in covalent histone modification/chromatin remodeling (34.5%) (MEN1, ARID1A, KMT2C and KMT2A were recurrently mutated) as well as DNA repair (17.2%) pathways. Unsupervised clustering and principle component analysis on gene expression and DNA methylation profiles showed 3 robust molecular subtypes (LC1, LC2, LC3) with distinct clinical features. MEN1 gene mutations were found to be enriched and exclusively in the LC2 subtype (p-value<0.001). The LC3 subtype is predominately found at endobronchial lung and earlier age of diagnosis. Immunohistochemical staining of two biomarkers, ASCL1 and S100, is sufficient to stratify the three subtypes. This molecular classification of lung carcinoids into three subtypes may help improve treatment decision and clinical management.
2019-07-01 | GSE118131 | GEO