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Identification of Candidate Serum Proteins for Classifying Well-Differentiated Small Intestinal Neuroendocrine Tumors

BACKGROUND: Patients with well-differentiated small intestine neuroendocrine tumors (WD-SI-NETs) are most often diagnosed at a metastatic stage of disease, which reduces possibilities for a curative treatment. Thus new approaches for earlier detection and improved monitoring of the disease are requi...

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Autores principales: Darmanis, Spyros, Cui, Tao, Drobin, Kimi, Li, Su-Chen, Öberg, Kjell, Nilsson, Peter, Schwenk, Jochen M., Giandomenico, Valeria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3839889/
https://www.ncbi.nlm.nih.gov/pubmed/24282616
http://dx.doi.org/10.1371/journal.pone.0081712
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author Darmanis, Spyros
Cui, Tao
Drobin, Kimi
Li, Su-Chen
Öberg, Kjell
Nilsson, Peter
Schwenk, Jochen M.
Giandomenico, Valeria
author_facet Darmanis, Spyros
Cui, Tao
Drobin, Kimi
Li, Su-Chen
Öberg, Kjell
Nilsson, Peter
Schwenk, Jochen M.
Giandomenico, Valeria
author_sort Darmanis, Spyros
collection PubMed
description BACKGROUND: Patients with well-differentiated small intestine neuroendocrine tumors (WD-SI-NETs) are most often diagnosed at a metastatic stage of disease, which reduces possibilities for a curative treatment. Thus new approaches for earlier detection and improved monitoring of the disease are required. MATERIALS AND METHODS: Suspension bead arrays targeting 124 unique proteins with antibodies from the Human Protein Atlas were used to profile biotinylated serum samples. Discoveries from a cohort of 77 individuals were followed up in a cohort of 132 individuals both including healthy controls as well as patients with untreated primary WD-SI-NETs, lymph node metastases and liver metastases. RESULTS: A set of 20 antibodies suggested promising proteins for further verification based on technically verified statistical significance. Proceeding, we assessed the classification performance in an independent cohort of patient serum, achieving, classification accuracy of up to 85% with different subsets of antibodies in respective pairwise group comparisons. The protein profiles of nine targets, namely IGFBP2, IGF1, SHKBP1, ETS1, IL1α, STX2, MAML3, EGR3 and XIAP were verified as significant contributors to tumor classification. CONCLUSIONS: We propose new potential protein biomarker candidates for classifying WD-SI-NETs at different stage of disease. Further evaluation of these proteins in larger sample sets and with alternative approaches is needed in order to further improve our understanding of their functional relation to WD-SI-NETs and their eventual use in diagnostics.
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spelling pubmed-38398892013-11-26 Identification of Candidate Serum Proteins for Classifying Well-Differentiated Small Intestinal Neuroendocrine Tumors Darmanis, Spyros Cui, Tao Drobin, Kimi Li, Su-Chen Öberg, Kjell Nilsson, Peter Schwenk, Jochen M. Giandomenico, Valeria PLoS One Research Article BACKGROUND: Patients with well-differentiated small intestine neuroendocrine tumors (WD-SI-NETs) are most often diagnosed at a metastatic stage of disease, which reduces possibilities for a curative treatment. Thus new approaches for earlier detection and improved monitoring of the disease are required. MATERIALS AND METHODS: Suspension bead arrays targeting 124 unique proteins with antibodies from the Human Protein Atlas were used to profile biotinylated serum samples. Discoveries from a cohort of 77 individuals were followed up in a cohort of 132 individuals both including healthy controls as well as patients with untreated primary WD-SI-NETs, lymph node metastases and liver metastases. RESULTS: A set of 20 antibodies suggested promising proteins for further verification based on technically verified statistical significance. Proceeding, we assessed the classification performance in an independent cohort of patient serum, achieving, classification accuracy of up to 85% with different subsets of antibodies in respective pairwise group comparisons. The protein profiles of nine targets, namely IGFBP2, IGF1, SHKBP1, ETS1, IL1α, STX2, MAML3, EGR3 and XIAP were verified as significant contributors to tumor classification. CONCLUSIONS: We propose new potential protein biomarker candidates for classifying WD-SI-NETs at different stage of disease. Further evaluation of these proteins in larger sample sets and with alternative approaches is needed in order to further improve our understanding of their functional relation to WD-SI-NETs and their eventual use in diagnostics. Public Library of Science 2013-11-25 /pmc/articles/PMC3839889/ /pubmed/24282616 http://dx.doi.org/10.1371/journal.pone.0081712 Text en © 2013 Darmanis et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Darmanis, Spyros
Cui, Tao
Drobin, Kimi
Li, Su-Chen
Öberg, Kjell
Nilsson, Peter
Schwenk, Jochen M.
Giandomenico, Valeria
Identification of Candidate Serum Proteins for Classifying Well-Differentiated Small Intestinal Neuroendocrine Tumors
title Identification of Candidate Serum Proteins for Classifying Well-Differentiated Small Intestinal Neuroendocrine Tumors
title_full Identification of Candidate Serum Proteins for Classifying Well-Differentiated Small Intestinal Neuroendocrine Tumors
title_fullStr Identification of Candidate Serum Proteins for Classifying Well-Differentiated Small Intestinal Neuroendocrine Tumors
title_full_unstemmed Identification of Candidate Serum Proteins for Classifying Well-Differentiated Small Intestinal Neuroendocrine Tumors
title_short Identification of Candidate Serum Proteins for Classifying Well-Differentiated Small Intestinal Neuroendocrine Tumors
title_sort identification of candidate serum proteins for classifying well-differentiated small intestinal neuroendocrine tumors
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3839889/
https://www.ncbi.nlm.nih.gov/pubmed/24282616
http://dx.doi.org/10.1371/journal.pone.0081712
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