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Heterogeneity analysis of the proteomes in clinically nonfunctional pituitary adenomas

BACKGROUND: Clinically nonfunctional pituitary adenomas (NFPAs) without any clinical elevation of hormone and with a difficulty in its early-stage diagnosis are highly heterogeneous with different hormone expressions in NFPA tissues, including luteinizing hormone (LH)-positive, follicle-stimulating...

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Autores principales: Zhan, Xianquan, Wang, Xiaowei, Long, Ying, Desiderio, Dominic M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4302698/
https://www.ncbi.nlm.nih.gov/pubmed/25539738
http://dx.doi.org/10.1186/s12920-014-0069-6
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author Zhan, Xianquan
Wang, Xiaowei
Long, Ying
Desiderio, Dominic M
author_facet Zhan, Xianquan
Wang, Xiaowei
Long, Ying
Desiderio, Dominic M
author_sort Zhan, Xianquan
collection PubMed
description BACKGROUND: Clinically nonfunctional pituitary adenomas (NFPAs) without any clinical elevation of hormone and with a difficulty in its early-stage diagnosis are highly heterogeneous with different hormone expressions in NFPA tissues, including luteinizing hormone (LH)-positive, follicle-stimulating hormone (FSH)-positive, LH/FSH-positive, and negative (NF). Elucidation of molecular mechanisms and discovery of biomarkers common and specific to those different subtypes of NFPAs will benefit NFPA patients in early-stage diagnosis and individualized treatment. METHODS: Two-dimensional gel electrophoresis (2DGE) and PDQuest image analyses were used to compare proteomes of different NFPA subtypes (NF-, LH-, FSH-, and LH/FSH-positive) relative to control pituitaries (Con). Differentially expressed proteins (DEPs) were characterized with mass spectrometry (MS). Each set of DEPs in four NFPA subtypes was evaluated with overlap analysis and signaling pathway network analysis with comparison to determine any DEP and pathway network that are common and specific to each NFPA subtype. RESULTS: A total of 93 differential protein-spots were determined with comparison of each NFPA type (NF-, LH-, FSH-, and LH/FSH-positive) versus control pituitaries. A total of 76 protein-spots were MS-identified (59 DEPs in NF vs. Con; 65 DEPs in LH vs. Con; 63 DEPs in FSH vs. Con; and 55 DEPs in LH/FSH vs. Con). A set of DEPs and pathway network data were common and specific to each NFPA subtype. Four important common pathway systems included MAPK-signaling abnormality, oxidative stress, mitochondrial dysfunction, and cell-cycle dysregulation. However, these pathway systems were, in fact, different among four NFPA subtypes with different protein-expression levels of most of nodes, different protein profiles, and different pathway network profiles. CONCLUSIONS: These result data demonstrate that common and specific DEPs and pathway networks exist in four NFPA subtypes, and clarify proteome heterogeneity of four NFPA subtypes. Those findings will help to elucidate molecular mechanisms of NFPAs, and discover protein biomarkers to effectively manage NFPA patients towards personalized medicine. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12920-014-0069-6) contains supplementary material, which is available to authorized users.
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spelling pubmed-43026982015-01-23 Heterogeneity analysis of the proteomes in clinically nonfunctional pituitary adenomas Zhan, Xianquan Wang, Xiaowei Long, Ying Desiderio, Dominic M BMC Med Genomics Research Article BACKGROUND: Clinically nonfunctional pituitary adenomas (NFPAs) without any clinical elevation of hormone and with a difficulty in its early-stage diagnosis are highly heterogeneous with different hormone expressions in NFPA tissues, including luteinizing hormone (LH)-positive, follicle-stimulating hormone (FSH)-positive, LH/FSH-positive, and negative (NF). Elucidation of molecular mechanisms and discovery of biomarkers common and specific to those different subtypes of NFPAs will benefit NFPA patients in early-stage diagnosis and individualized treatment. METHODS: Two-dimensional gel electrophoresis (2DGE) and PDQuest image analyses were used to compare proteomes of different NFPA subtypes (NF-, LH-, FSH-, and LH/FSH-positive) relative to control pituitaries (Con). Differentially expressed proteins (DEPs) were characterized with mass spectrometry (MS). Each set of DEPs in four NFPA subtypes was evaluated with overlap analysis and signaling pathway network analysis with comparison to determine any DEP and pathway network that are common and specific to each NFPA subtype. RESULTS: A total of 93 differential protein-spots were determined with comparison of each NFPA type (NF-, LH-, FSH-, and LH/FSH-positive) versus control pituitaries. A total of 76 protein-spots were MS-identified (59 DEPs in NF vs. Con; 65 DEPs in LH vs. Con; 63 DEPs in FSH vs. Con; and 55 DEPs in LH/FSH vs. Con). A set of DEPs and pathway network data were common and specific to each NFPA subtype. Four important common pathway systems included MAPK-signaling abnormality, oxidative stress, mitochondrial dysfunction, and cell-cycle dysregulation. However, these pathway systems were, in fact, different among four NFPA subtypes with different protein-expression levels of most of nodes, different protein profiles, and different pathway network profiles. CONCLUSIONS: These result data demonstrate that common and specific DEPs and pathway networks exist in four NFPA subtypes, and clarify proteome heterogeneity of four NFPA subtypes. Those findings will help to elucidate molecular mechanisms of NFPAs, and discover protein biomarkers to effectively manage NFPA patients towards personalized medicine. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12920-014-0069-6) contains supplementary material, which is available to authorized users. BioMed Central 2014-12-24 /pmc/articles/PMC4302698/ /pubmed/25539738 http://dx.doi.org/10.1186/s12920-014-0069-6 Text en © Zhan et al.; licensee BioMed Central. 2014 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Zhan, Xianquan
Wang, Xiaowei
Long, Ying
Desiderio, Dominic M
Heterogeneity analysis of the proteomes in clinically nonfunctional pituitary adenomas
title Heterogeneity analysis of the proteomes in clinically nonfunctional pituitary adenomas
title_full Heterogeneity analysis of the proteomes in clinically nonfunctional pituitary adenomas
title_fullStr Heterogeneity analysis of the proteomes in clinically nonfunctional pituitary adenomas
title_full_unstemmed Heterogeneity analysis of the proteomes in clinically nonfunctional pituitary adenomas
title_short Heterogeneity analysis of the proteomes in clinically nonfunctional pituitary adenomas
title_sort heterogeneity analysis of the proteomes in clinically nonfunctional pituitary adenomas
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4302698/
https://www.ncbi.nlm.nih.gov/pubmed/25539738
http://dx.doi.org/10.1186/s12920-014-0069-6
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