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Transcriptional changes associated with functioning and non-functioning Pituitary adenomas.

ABSTRACT: Transcriptional changes associated with functioning and non-functioning Pituitary adenomas.

PROVIDER: PRJNA831798 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18911609_1.fastq.gz	Fastqsanger.gz
	SRR18911609_2.fastq.gz	Fastqsanger.gz
	SRR18911610_1.fastq.gz	Fastqsanger.gz
	SRR18911610_2.fastq.gz	Fastqsanger.gz
	SRR18911611_1.fastq.gz	Fastqsanger.gz

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Project description:<p>Pituitary adenomas constitute 10 to 25% of intracranial tumors, rendering them one of the most prevalent types of brain tumors. While the majority of pituitary adenomas are benign, ~35% exhibit invasive behavior. Compared with their non-invasive counterparts, invasive pituitary adenomas are more challenging to manage, highlighting the need to elucidate their underlying pathogenesis. However, the molecular mechanisms driving the invasive behavior of these tumors remain incompletely understood. Thus, the present study employed an integrated proteomic and metabolomic approach to investigate the molecular features associated with tumor invasiveness in pituitary adenomas. The investigation was performed at the First Affiliated Hospital of Xiamen University (Xiamen, China). Fresh-frozen tumor specimens were collected from 16 patients diagnosed with clinically non-functioning pituitary adenomas. These samples were divided into two groups based on invasiveness: Invasive tumors (n=8; Knosp grade ≥2) and non-invasive tumors (n=8; Knosp grade <2). Using data-independent acquisition mass spectrometry (MS) in conjunction with liquid chromatography-MS/MS metabolomics analysis, differentially expressed proteins (DEPs) and metabolites (DEMs) were identified. Comparative analysis identified 614 DEPs, including 286 proteins that were upregulated and 328 that were downregulated in invasive relative to non-invasive tumors. Additionally, 74 DEMs were found, comprising 42 increased and 32 decreased metabolites. Enrichment analysis of pathways revealed notable involvement of the cyclic adenosine monophosphate (cAMP) signaling cascade, pathways related to pathogenic Escherichia coli (E. coli) infection and the synaptic vesicle cycle. Integration of the proteomic and metabolomic data underscored consistent changes within these biological pathways. The present investigation represents a comprehensive effort to combine proteomic and metabolomic approaches to characterize the invasive phenotype of pituitary adenomas. The identification of enriched pathways associated with cAMP signaling, E. coli infection and synaptic vesicle cycling provides new mechanistic understanding and offers potential biomarkers or therapeutic targets for differentiating tumor aggressiveness. </p>

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).

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Transcriptional changes associated with functioning and non-functioning Pituitary adenomas.

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