Heterogeneity analysis of the proteomes in clinically nonfunctional pituitary adenomas

BMC Medical Genomics

Dominic M Desiderio²  Ying Long¹  Xiaowei Wang¹  Xianquan Zhan³ 

[1] State Local Joint Engineering Laboratory for Anticancer Drugs, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, Hunan, P. R. China;The Charles B. Stout Neuroscience Mass Spectrometry Laboratory, Department of Neurology, College of Medicine, University of Tennessee Health Science Center, 847 Monroe Avenue, Memphis 38163, TN, USA;The State Key Laboratory of Medical Genetics, Central South University, 88 Xiangya Road, Changsha 410008, Hunan, P. R. China

关键词: Pathway network;    Differentially expressed protein;    Mass spectrometry;    Two-dimensional gel electrophoresis;    Heterogeneity;    Proteome;    Nonfunctional pituitary adenoma;   

Others  :  1090084
DOI  :  10.1186/s12920-014-0069-6

 received in 2014-10-03, accepted in 2014-12-11,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Zhan et al.; licensee BioMed Central.

【 图 表 】

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