Quantitative proteomic analysis of prostate tissue specimens identifies deregulated protein complexes in primary prostate cancer

BACKGROUND: Prostate cancer (PCa) is the most frequently diagnosed non-skin cancer and a leading cause of mortality among males in developed countries. However, our understanding of the global changes of protein complexes within PCa tissue specimens remains very limited, although it has been well re...

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Autores principales: Zhou, Bo, Yan, Yiwu, Wang, Yang, You, Sungyong, Freeman, Michael R., Yang, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6461817/
https://www.ncbi.nlm.nih.gov/pubmed/31011308
http://dx.doi.org/10.1186/s12014-019-9236-2
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author Zhou, Bo
Yan, Yiwu
Wang, Yang
You, Sungyong
Freeman, Michael R.
Yang, Wei
author_facet Zhou, Bo
Yan, Yiwu
Wang, Yang
You, Sungyong
Freeman, Michael R.
Yang, Wei
author_sort Zhou, Bo
collection PubMed
description BACKGROUND: Prostate cancer (PCa) is the most frequently diagnosed non-skin cancer and a leading cause of mortality among males in developed countries. However, our understanding of the global changes of protein complexes within PCa tissue specimens remains very limited, although it has been well recognized that protein complexes carry out essentially all major processes in living organisms and that their deregulation drives the pathogenesis and progression of various diseases. METHODS: By coupling tandem mass tagging-synchronous precursor selection-mass spectrometry/mass spectrometry/mass spectrometry with differential expression and co-regulation analyses, the present study compared the differences between protein complexes in normal prostate, low-grade PCa, and high-grade PCa tissue specimens. RESULTS: Globally, a large downregulated putative protein–protein interaction (PPI) network was detected in both low-grade and high-grade PCa, yet a large upregulated putative PPI network was only detected in high-grade but not low-grade PCa, compared with normal controls. To identify specific protein complexes that are deregulated in PCa, quantified proteins were mapped to protein complexes in CORUM (v3.0), a high-quality collection of 4274 experimentally verified mammalian protein complexes. Differential expression and gene ontology (GO) enrichment analyses suggested that 13 integrin complexes involved in cell adhesion were significantly downregulated in both low- and high-grade PCa compared with normal prostate, and that four Prothymosin alpha (ProTα) complexes were significantly upregulated in high-grade PCa compared with normal prostate. Moreover, differential co-regulation and GO enrichment analyses indicated that the assembly levels of six protein complexes involved in RNA splicing were significantly increased in low-grade PCa, and those of four subcomplexes of mitochondrial complex I were significantly increased in high-grade PCa, compared with normal prostate. CONCLUSIONS: In summary, to the best of our knowledge, the study represents the first large-scale and quantitative, albeit indirect, comparison of individual protein complexes in human PCa tissue specimens. It may serve as a useful resource for better understanding the deregulation of protein complexes in primary PCa. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12014-019-9236-2) contains supplementary material, which is available to authorized users.
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spelling pubmed-64618172019-04-22 Quantitative proteomic analysis of prostate tissue specimens identifies deregulated protein complexes in primary prostate cancer Zhou, Bo Yan, Yiwu Wang, Yang You, Sungyong Freeman, Michael R. Yang, Wei Clin Proteomics Research BACKGROUND: Prostate cancer (PCa) is the most frequently diagnosed non-skin cancer and a leading cause of mortality among males in developed countries. However, our understanding of the global changes of protein complexes within PCa tissue specimens remains very limited, although it has been well recognized that protein complexes carry out essentially all major processes in living organisms and that their deregulation drives the pathogenesis and progression of various diseases. METHODS: By coupling tandem mass tagging-synchronous precursor selection-mass spectrometry/mass spectrometry/mass spectrometry with differential expression and co-regulation analyses, the present study compared the differences between protein complexes in normal prostate, low-grade PCa, and high-grade PCa tissue specimens. RESULTS: Globally, a large downregulated putative protein–protein interaction (PPI) network was detected in both low-grade and high-grade PCa, yet a large upregulated putative PPI network was only detected in high-grade but not low-grade PCa, compared with normal controls. To identify specific protein complexes that are deregulated in PCa, quantified proteins were mapped to protein complexes in CORUM (v3.0), a high-quality collection of 4274 experimentally verified mammalian protein complexes. Differential expression and gene ontology (GO) enrichment analyses suggested that 13 integrin complexes involved in cell adhesion were significantly downregulated in both low- and high-grade PCa compared with normal prostate, and that four Prothymosin alpha (ProTα) complexes were significantly upregulated in high-grade PCa compared with normal prostate. Moreover, differential co-regulation and GO enrichment analyses indicated that the assembly levels of six protein complexes involved in RNA splicing were significantly increased in low-grade PCa, and those of four subcomplexes of mitochondrial complex I were significantly increased in high-grade PCa, compared with normal prostate. CONCLUSIONS: In summary, to the best of our knowledge, the study represents the first large-scale and quantitative, albeit indirect, comparison of individual protein complexes in human PCa tissue specimens. It may serve as a useful resource for better understanding the deregulation of protein complexes in primary PCa. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12014-019-9236-2) contains supplementary material, which is available to authorized users. BioMed Central 2019-04-13 /pmc/articles/PMC6461817/ /pubmed/31011308 http://dx.doi.org/10.1186/s12014-019-9236-2 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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
Zhou, Bo
Yan, Yiwu
Wang, Yang
You, Sungyong
Freeman, Michael R.
Yang, Wei
Quantitative proteomic analysis of prostate tissue specimens identifies deregulated protein complexes in primary prostate cancer
title Quantitative proteomic analysis of prostate tissue specimens identifies deregulated protein complexes in primary prostate cancer
title_full Quantitative proteomic analysis of prostate tissue specimens identifies deregulated protein complexes in primary prostate cancer
title_fullStr Quantitative proteomic analysis of prostate tissue specimens identifies deregulated protein complexes in primary prostate cancer
title_full_unstemmed Quantitative proteomic analysis of prostate tissue specimens identifies deregulated protein complexes in primary prostate cancer
title_short Quantitative proteomic analysis of prostate tissue specimens identifies deregulated protein complexes in primary prostate cancer
title_sort quantitative proteomic analysis of prostate tissue specimens identifies deregulated protein complexes in primary prostate cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6461817/
https://www.ncbi.nlm.nih.gov/pubmed/31011308
http://dx.doi.org/10.1186/s12014-019-9236-2
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