Label-free LC-MSe in tissue and serum reveals protein networks underlying differences between benign and malignant serous ovarian tumors.

<h4>Purpose</h4>To identify proteins and (molecular/biological) pathways associated with differences between benign and malignant epithelial ovarian tumors.<h4>Experimental procedures</h4>Serum of six patients with a serous adenocarcinoma of the ovary was collected before tre...

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Autores principales:	Wouter Wegdam, Carmen A Argmann, Gertjan Kramer, Johannes P Vissers, Marrije R Buist, Gemma G Kenter, Johannes M F G Aerts, Danielle Meijer, Perry D Moerland
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/034990b2eb1c49cca4433dc419d364d4
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spelling	oai:doaj.org-article:034990b2eb1c49cca4433dc419d364d42021-11-25T05:58:52ZLabel-free LC-MSe in tissue and serum reveals protein networks underlying differences between benign and malignant serous ovarian tumors.1932-620310.1371/journal.pone.0108046https://doaj.org/article/034990b2eb1c49cca4433dc419d364d42014-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0108046https://doaj.org/toc/1932-6203<h4>Purpose</h4>To identify proteins and (molecular/biological) pathways associated with differences between benign and malignant epithelial ovarian tumors.<h4>Experimental procedures</h4>Serum of six patients with a serous adenocarcinoma of the ovary was collected before treatment, with a control group consisting of six matched patients with a serous cystadenoma. In addition to the serum, homogeneous regions of cells exhibiting uniform histology were isolated from benign and cancerous tissue by laser microdissection. We subsequently employed label-free liquid chromatography tandem mass spectrometry (LC-MSe) to identify proteins in these serum and tissues samples. Analyses of differential expression between samples were performed using Bioconductor packages and in-house scripts in the statistical software package R. Hierarchical clustering and pathway enrichment analyses were performed, as well as network enrichment and interactome analysis using MetaCore.<h4>Results</h4>In total, we identified 20 and 71 proteins that were significantly differentially expressed between benign and malignant serum and tissue samples, respectively. The differentially expressed protein sets in serum and tissue largely differed with only 2 proteins in common. MetaCore network analysis, however inferred GCR-alpha and Sp1 as common transcriptional regulators. Interactome analysis highlighted 14-3-3 zeta/delta, 14-3-3 beta/alpha, Alpha-actinin 4, HSP60, and PCBP1 as critical proteins in the tumor proteome signature based on their relative overconnectivity. The data have been deposited to the ProteomeXchange with identifier PXD001084.<h4>Discussion</h4>Our analysis identified proteins with both novel and previously known associations to ovarian cancer biology. Despite the small overlap between differentially expressed protein sets in serum and tissue, APOA1 and Serotransferrin were significantly lower expressed in both serum and cancer tissue samples, suggesting a tissue-derived effect in serum. Pathway and subsequent interactome analysis also highlighted common regulators in serum and tissue samples, suggesting a yet unknown role for PCBP1 in ovarian cancer pathophysiology.Wouter WegdamCarmen A ArgmannGertjan KramerJohannes P VissersMarrije R BuistGemma G KenterJohannes M F G AertsDanielle MeijerPerry D MoerlandPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 9, p e108046 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Wouter Wegdam Carmen A Argmann Gertjan Kramer Johannes P Vissers Marrije R Buist Gemma G Kenter Johannes M F G Aerts Danielle Meijer Perry D Moerland Label-free LC-MSe in tissue and serum reveals protein networks underlying differences between benign and malignant serous ovarian tumors.
description	<h4>Purpose</h4>To identify proteins and (molecular/biological) pathways associated with differences between benign and malignant epithelial ovarian tumors.<h4>Experimental procedures</h4>Serum of six patients with a serous adenocarcinoma of the ovary was collected before treatment, with a control group consisting of six matched patients with a serous cystadenoma. In addition to the serum, homogeneous regions of cells exhibiting uniform histology were isolated from benign and cancerous tissue by laser microdissection. We subsequently employed label-free liquid chromatography tandem mass spectrometry (LC-MSe) to identify proteins in these serum and tissues samples. Analyses of differential expression between samples were performed using Bioconductor packages and in-house scripts in the statistical software package R. Hierarchical clustering and pathway enrichment analyses were performed, as well as network enrichment and interactome analysis using MetaCore.<h4>Results</h4>In total, we identified 20 and 71 proteins that were significantly differentially expressed between benign and malignant serum and tissue samples, respectively. The differentially expressed protein sets in serum and tissue largely differed with only 2 proteins in common. MetaCore network analysis, however inferred GCR-alpha and Sp1 as common transcriptional regulators. Interactome analysis highlighted 14-3-3 zeta/delta, 14-3-3 beta/alpha, Alpha-actinin 4, HSP60, and PCBP1 as critical proteins in the tumor proteome signature based on their relative overconnectivity. The data have been deposited to the ProteomeXchange with identifier PXD001084.<h4>Discussion</h4>Our analysis identified proteins with both novel and previously known associations to ovarian cancer biology. Despite the small overlap between differentially expressed protein sets in serum and tissue, APOA1 and Serotransferrin were significantly lower expressed in both serum and cancer tissue samples, suggesting a tissue-derived effect in serum. Pathway and subsequent interactome analysis also highlighted common regulators in serum and tissue samples, suggesting a yet unknown role for PCBP1 in ovarian cancer pathophysiology.
format	article
author	Wouter Wegdam Carmen A Argmann Gertjan Kramer Johannes P Vissers Marrije R Buist Gemma G Kenter Johannes M F G Aerts Danielle Meijer Perry D Moerland
author_facet	Wouter Wegdam Carmen A Argmann Gertjan Kramer Johannes P Vissers Marrije R Buist Gemma G Kenter Johannes M F G Aerts Danielle Meijer Perry D Moerland
author_sort	Wouter Wegdam
title	Label-free LC-MSe in tissue and serum reveals protein networks underlying differences between benign and malignant serous ovarian tumors.
title_short	Label-free LC-MSe in tissue and serum reveals protein networks underlying differences between benign and malignant serous ovarian tumors.
title_full	Label-free LC-MSe in tissue and serum reveals protein networks underlying differences between benign and malignant serous ovarian tumors.
title_fullStr	Label-free LC-MSe in tissue and serum reveals protein networks underlying differences between benign and malignant serous ovarian tumors.
title_full_unstemmed	Label-free LC-MSe in tissue and serum reveals protein networks underlying differences between benign and malignant serous ovarian tumors.
title_sort	label-free lc-mse in tissue and serum reveals protein networks underlying differences between benign and malignant serous ovarian tumors.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/034990b2eb1c49cca4433dc419d364d4
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Label-free LC-MSe in tissue and serum reveals protein networks underlying differences between benign and malignant serous ovarian tumors.

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