Growth Hormone (GH) -secreting Pituitary Adenoma
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ABSTRACT:
PROVIDER: EGAS00001001293 | EGA |
REPOSITORIES: EGA
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Project description:We profiled the somatic landscape of 21 growth hormone (GH) -secreting pituitary adenomas using somatic copy-number alteration (SCNA), whole-genome sequencing (WGS), bisulfate sequencing, and transcriptome approaches. See details in Valimaki et al. Genetic and epigenetic characterization of growth hormone (GH) - secreting pituitary tumors. Manuscript in preparation, 2019.
| EGAS00001003488 | EGA
Project description:Objective Circulating plasma miRNAs have been increasingly studied in the field of pituitary neuroendocrine tumor (PitNET) research. Our aim was to discover circulating plasma miRNAs species associated with growth hormone (GH) secreting PitNETs and assess how the plasma levels of discovered miRNA candidates are impacted by SSA therapy and whether there is a difference in their levels between GH secreting PitNETs and other PitNET types. Methods miRNA candidates were discovered using the whole miRNA sequencing approach and differential expression analysis. Selected miRNAs were then analyzed using real-time polymerase chain reaction (qPCR). Results Whole miRNA sequencing discovered a total of 19 differentially expressed miRNAs (DEMs) in GH secreting PitNET patients' plasma 24 hours after surgery and 19 DEMs between GH secreting PitNET patients’ plasma and non-functioning (NF) PitNET patients’ plasma. Seven miRNAs were selected for further testing of which miR-625-5p, miR-503-5p miR-181a-2-3p and miR-130b-3p showed a significant downregulation in plasma after 1 month of SSA treatment. miR-181a-5p and mir-625-5p were also found to be significantly downregulated in plasma of GH secreting PitNET patients vs. NF PitNET patients. Conclusions Our study suggests that expression of plasma miRNAs miR-625-5p, miR-503-5p miR-181a-2-3p and miR-130b-3p in GH secreting PitNETs is affected by SSA treatment. Additionally, miR-625-5p and miR-181a-5p can distinguish GH secreting PitNETs from other PitNET types warranting further research on these miRNAs for treatment efficacy.
2022-02-16 | GSE196647 | GEO
Project description:This study investigated differential gene expression between granulation patterns in growth hormone (GH)-secreting pituitary tumors, aiming to elucidate novel transcriptomes that explain clinical variances in patients with acromegaly. Transcriptome analysis was conducted on 6 normal pituitary tissues and 15 GH-secreting pituitary tumors, including 9 densely granulated somatotroph tumors (DGSTs) and 6 sparsely granulated somatotroph tumors (SGSTs). We identified 3111 differentially expressed genes (DEGs) in tumors compared to normal pituitaries, with 1117 DEGs unique to a specific granulation within tumors. SGST showed enrichment of neuronal development and acute inflammatory response pathways, along with a significant enhancement of JAK–STAT, phosphatidylinositol 3-kinase, and MAPK signaling. The results suggest that granulation-specific gene expression may underpin diverse clinical presentations in acromegaly, highlighting the potential for further investigation into these transcriptomic variations and their roles in disease pathology, particularly the involvement of genes linked to neuronal development, inflammatory response, and JAK–STAT signaling in SGST.
2024-04-28 | GSE264621 | GEO
Project description:Acromegaly is a severe and life-threatening disease caused by persistent excess of growth hormone (GH) which stimulates the synthesis and secretion of insulin-like growth factor-1 (IGF-1). In the majority (95%) of patients acromegaly is caused by sporadic GH-secreting neuroendocrine pituitary tumor (PitNET). Acromegaly-causing tumors are histologically diverse. The aim was to determine transcriptomic profiles in different histological subtypes and evaluate clinical implication of differential gene expression.
2022-12-01 | E-MTAB-11889 | biostudies-arrayexpress
Project description:Recurrent single-nucleotide and small indel somatic mutations were infrequent among the three adenoma subtypes. However, somatic copy-number alterations (SCNA) were identified in all three pituitary adenoma subtypes. Methylation analysis revealed adenoma subtype-specific DNA methylation profiles, with GHsecreting adenomas being dominated by hypomethylated sites. Likewise, gene-expression patterns revealed adenoma subtype-specific profiles. Integrating DNA methylation and gene-expression data revealed that hypomethylation of promoter regions are related with increased expression of GH1 and SSTR5 genes in GH-secreting adenomas and POMC gene in ACTH secreting adenomas. Finally, multispectral IHC staining of immune-related proteins showed abundant expression of PD-L1 among all three adenoma subtypes.
2020-03-26 | GSE147548 | GEO
Project description:Gene alteration analysis on 121 GH-producing pituitary adenomas and non-target proteomics analysis with RNA sequencing analysis on 45 non-functioning pituitary adenomas (NFPAs) and 60 growth hormone (GH)-producing pituitary adenomas were performed, and integrated these results with the clinical characteristics of acromegaly. We attempted to identify key players involved in shaping the clinical features of acromegaly, especially those related to treatment efficacy. This project revealed the importance of GNAS mutations in terms of clinical and biochemical characteristics and identified novel molecules that may be involved in the responsiveness to medical treatment.
2022-11-24 | PXD036604 | JPOST Repository
Project description:Growth hormone receptor deficiency (GHRD) results in low serum insulin-like growth factor 1 but high, non-functional GH levels. This study investigates the histomorphological and molecular alterations associated with GHRD. Pituitary glands from 6 months old GHR-KO pigs and control animals were compared using a quantitative stereological approach and label-free proteomics.
2023-05-12 | PXD035833 | Pride
Project description:Despite a considerable literature concerning the molecular pathogenesis of pituitary tumors, the mechanisms of pituitary tumors development and progression remain unknown. Four SAGE cDNA libraries were constructed using a pool of mRNA obtained from five GH-, two ACTH-secreting, and four non secreting pituitary tumors (NS), and three normal pituitaries from patients who had accidental death, using I-SAGE kit (Invitrogen). The aim of this study was to evaluate the differential gene expression profile by SAGE genes in different subtypes of pituitary tumors to contribute for understanding of pituitary tumorigenesis. Comparative analysis of gene expression profiles in subtypes of pituitary tumores.
2014-04-10 | E-GEOD-37153 | biostudies-arrayexpress
Project description:Background: Growth hormone-secreting pituitary adenoma (GHPA) is an insidious disease with persistent hypersecretion of growth hormone and insulin-like growth factor 1, leading to increased morbidity and mortality. Though treatments for GHPA have greatly improved, lack of deep knowledge on the precise molecular mechanisms involved in GHPA hinders the development of therapeutic approaches. Few studies have attempted to reveal the genome-wide landscape of GHPA. As chromatin structure change exerts significant influence on gene transcription, herein, we investigated the landscape of chromatin accessibility. Methods: Both assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) and RNA sequencing (RNA-seq) were applied to identify the differential expression genes (DEGs) and uncover chromatin accessibility changes and the potentially associated transcription factor (TFs) in somatotropinoma tissues. Results: 64 DEGs were obtained, including 10 DEGs were elevated in the tumors and 54 DEGs were negligibly expressed in adenomas. A total of 3916 increased and 2895 decreased chromatin-accessible regions were identified nearby these DEGs. The majority of DEGs associated with closed chromatin regions were significantly down-regulated in our study, while the most of DEGs near open chromatin were not expectantly up-regulated. Additionally, the newly opened and closed chromatin regions were highly enriched for GRE and CTCF transcription factor binding sites, which were potentially relevant to the regulation of chromatin accessibility and genes expression in GHPA. Conclusion: Collectively, our results reveal the landscape of chromatin accessibility and unique enhancer in GHPA, which may, at least in part, contribute to tumorigenesis and provide a new field of drug development.
2021-08-18 | GSE182180 | GEO
Project description:Despite a considerable literature concerning the molecular pathogenesis of pituitary tumors, the mechanisms of pituitary tumors development and progression remain unknown. Four SAGE cDNA libraries were constructed using a pool of mRNA obtained from five GH-, two ACTH-secreting, and four non secreting pituitary tumors (NS), and three normal pituitaries from patients who had accidental death, using I-SAGE kit (Invitrogen). The aim of this study was to evaluate the differential gene expression profile by SAGE genes in different subtypes of pituitary tumors to contribute for understanding of pituitary tumorigenesis.
2014-04-10 | GSE37153 | GEO