The differential gene screening for invasive pituitary adenoma and non-invasive pituitary adenoma
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE260487 | GEO | 2024/03/04
REPOSITORIES: GEO
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Project description:Pituitary adenomas are common benign neoplasms giving rise to disorders of growth, reproductive function and cortisol production. Although recently determined to be monoclonal, very little is known about the mechanisms regulating the development of pituitary hyperplasia and neoplasia in humans. Surgical resection is the treatment of choice for most symptomatic pituitary adenomas. The goal of surgery is the complete removal of the tumor and the success of surgery is strongly affected by the presence of local invasion. However, complete tumor removal is unlikely when there is extensive local invasion. Identifying genes that control the invasiveness and recurrence of this class of tumors will provide therapeutic targets for this class of tumors. We will determine the expression pattern of genes in recurrent and invasive and pituitary adenomas and compare those to non-invasive and non-recurrent tumors. We hypothesize that the differential expression and activation of a number of genes affect pituitary adenoma recurrence and invasiveness. Rationale: Preliminary result showed a differential expression of novel PKC isozymes in non-invasive and invasive pituitary adenomas. PMA, an activator of both novel and classical PKC isozymes increased the expression of gelatinase A (MMP-2) mRNA in human pituitary adenoma cell line. This result raises a fundamental question as to the functional role of novel PKC isozymes and proteases in the invasive phenotype of pituitary adenomas. The primary component of this Specific Aim is to determine whether specific genes are differentially expressed in recurrent or invasive adenomas when compared with control non-invasive tumors. Tissue specimens from non-invasive and invasive (dural invasion based microscopic examination) and recurrent vs non-recurrent tumors will be used for microarray analysis. Frozen pituitaryspecimens will be collected and total RNA extracted with TriZol reagent. We will provide total RNA (10 ug) from non-invasive, invasive, reoccurred and non-occurrent pituitary adenomas.
2008-06-12 | E-GEOD-4237 | biostudies-arrayexpress
Project description:We collected samples from patients with invasive and non-invasive pituitary adenomas from Beijing Tiantan Hospital for protein extraction and quantitative analysis, and identified invasive differential proteins (DEPs) by differential analysis of the two groups.
2023-02-24 | PXD039328 | Pride
Project description:Context : Non Functioning Pituitary Adenomas (NFPAs), although typically benign, may be locally invasive. Few datas are currently available related to the molecular process of invasion in sporadic pituitary adenomas. Markers of invasiveness, important for helping the clinician in the therapeutic strategy particularly in the decision for adjuvant radiotherapy, are currently lacking. Objective: Evaluate if invasive NFPAs display a specific expression profile compared with non invasive tumors. Methods: To address this issue, we selected 40 NFPAs (38 of the gonadotroph type) and classified them as invasive (n=22) or non invasive (n=18) on the basis of MRI and surgical findings. Then we performed pangenomic analysis based on Agilent Human Whole genome Gene Expression oligonucleotide microarray (44k) Expression in order to identify genes differentially expressed between invasive and non invasive NFPA. Experiements are made in dual color with tumor samples labelled in cyanine 5 and a pool of all tumors labelled in cyanine 3.The expressions of some genes identified by microarray screening were confirmed by real-time quantitative RT-PCR. The selection of genes was made on the basis of Ingenuity networks and degree of upregulation between invasive and non invasive tumors. Moreover, some genes of interest already described in the literature were added to the analysis. Results: Prediction class analysis showed that 346 genes discriminated between invasive and non invasive NFPAs (p<0.001); 233 were up- and 113 were down-regulated between the two groups. We then tested On the basis of Ingenuity networks and degree of upregulation between invasive and non invasive tumors, a set of eight genes, including MYO5A, IGFBP5, FLT3, NFE2L1, PTTG, MMP9, NCAM and NR1H3, was tested in quantitative PCR analysis and. Results confirmed those obtained in microarrays results.analysis. At the protein level, Myosin 5A (MYO5A) demonstrated stronger immunostaining in invasive NFPAs compared to non invasive NFPAs. Conclusions: We propose a molecular signature of eight genes of grossly invasive NFPAs as compared with non invasive tumors: The product of one of these genes, MYO5A, may be a useful marker of invasive process in tumoral specimens. The role of these genes in the invasiveness process and as prognostic markers of pituitary adenomas needs to be confirmedinvestigated. Method: Microarray analyses the transcriptome of 22 invasive Non Functional Pituitary Adenomas (NFPAs) and 18 non invasive NFPAs in dual color (each sample labelled in cyanine 5 and a pool of all tumors labelled in cyanine 3).
2010-03-18 | E-TABM-899 | biostudies-arrayexpress
Project description:Corticotropin (ACTH)-secreting pituitary adenomas give rise to a severe endocrinological disorder, i.e., Cushing’s disease, with multifaceted clinical presentation and treatment outcomes. Experimental studies suggested that disease variability is inherent to the pituitary tumor, thus pointing to the need for further studies into tumor biology. Aim of the present study was to evaluate transcriptome expression pattern in a large series of ACTH-secreting pituitary adenoma specimens, in order to identify molecular signatures of these tumors. Gene expression profiling of formalin-fixed paraffin-embedded specimens from 40 human ACTH-secreting pituitary adenomas revealed significant expression of genes involved in protein biosynthesis and ribosomal function, in keeping with neuroendocrine cell profile. Unsupervised cluster analysis identified three distinct gene profile clusters and several genes were uniquely overexpressed in a given cluster, accounting for different molecular signatures. Of note, gene expression profiles were associated with clinical features such as age and size of the tumor. Altogether, our study shows that corticotrope tumors are characterized by neuroendocrine gene expression profile and present subgroup-specific molecular features.
2018-06-18 | GSE93825 | GEO
Project description:The incomplete surgical resection of invasive non-functional pituitary adenomas (iNFPAs) carries the increased risk of complications and requires adjuvant radiotherapy and medications. Thus, the molecular mechanisms and markers of invasiveness must be identified to guide the management of NFPA patients. This study explores the proteomic and transcriptomic variations of invasive and non-invasive NFPAs and other types of pituitary adenomas and evaluates the genetic markers in the exosome related to iNFPAs. The exosome from invasive and non-invasive NFPAs, prolactinomas (PRLs), growth hormone–secreting adenomas (GHs), adrenocorticotropic hormone-secreting adenomas (ACTHs), and normal pituitary tissue were analyzed. We confirmed that elevated matrix metalloproteinase-1 (MMP1) expression and its production in the exosome (exo-MMP1) are correlated with the invasive characteristics of NFPA. To investigate the molecular mechanism underlying the role of exo-MMP1 in invasiveness, we analyzed the effects of MMP1 on cell migration, cell growth and tumor angiogenesis. After transfection of MMP1 or a shRNA expression vector into NFPA cells, we obtained the associated exosome and observed that the altered expression and production of MMP1 in the exosome was significantly synchronized with the transduction of NFPA cells. In addition, the enrichment of MMP1 in the exosome promoted cell migration, cell growth and tumor angiogenesis via protease-activated receptor-1 (PAR1) signaling in recipient cells. Thus, these data demonstrate that MMP1 plays an important role in tumor invasion and angiogenesis and show that an exosome-mediated regulatory pathway for MMP1 may represent a target for therapeutic treatment.
2016-11-12 | GSE89779 | GEO
Project description:Background: Circulating miRNAs in pituitary adenoma would help patient care especially in non-functioning adenoma cases as minimally invasive biomarkers of tumor recurrence and progression. Aim: Our aim was to investigate plasma miRNA profile in patients with pituitary adenoma. Materials and Methods: 149 plasma and extracellular vesicle (preoperative, early- and late postoperative) samples were collected from 45 pituitary adenoma patients. Adenomas were characterized based on anterior pituitary hormones and transcription factors by immunostaining. MiRNA next generation sequencing was performed on 36 samples (discovery set). Individual TaqMan assay was used for validation on extended sample set. PA tissue miRNAs were evaluated by TaqMan array and literature data. Results: Global downregulation of miRNA expression was observed in plasma samples of pituitary adenoma patients compared to normal samples. Expression of 29 miRNAs and isomiR variants were able to distinguish preoperative plasma samples and normal controls. MiRNAs with altered expression in both plasma and different adenoma tissues were identified. 3, 7 and 66 miRNAs expressed differentially between preoperative and postoperative plasma samples in growth hormone secreting, FSH/LH+ and hormone-immunonegative groups, respectively. MiR-143-3p was downregulated in late- but not in early postoperative plasma samples compared to preoperative ones exclusively in FSH/LH+ adenomas. Plasma level of miR-143-3p discriminated these samples with 81.8% sensitivity and 72.3% specificity (AUC=0.79; p=0.02). Conclusions: Differentially expressed miRNAs in pituitary adenoma tissues have low abundance in plasma minimizing their role as biomarkers. Plasma miR-143-3p decreases in patients with FSH/LH+ adenoma indicated successful surgery, but its application for evaluating tumor recurrence needs further investigation.
2019-05-21 | GSE131483 | GEO
Project description:Aspirin, is a commonly used non-steroidal anti-inflammatory drug with antipyretic, analgesic, anti-inflammatory, and anti-thrombotic effect. Its antitumoral effect was also demonstrated in several cancer types. In this study our aim was to investigate the genomic effects of ASA in pituitary adenomas using high-throughput profiling approaches and validate our findings by targeted methodologies, using in vitro functional assays. Whole transcriptome profile of RC4-B/C and GH3 pituitary cell lines upon Aspirin treatment was investigated.
2022-06-19 | GSE202934 | 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:LncRNA-mRNA expression pattern in invasive pituitary adenomas: A microarray analysis
| PRJNA789793 | ENA
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