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Exploratory plasma proteomic analysis in a randomized crossover trial of aspirin among healthy men and women

Long-term use of aspirin is associated with lower risk of colorectal cancer and other cancers; however, the mechanism of chemopreventive effect of aspirin is not fully understood. Animal studies suggest that COX-2, NFκB signaling and Wnt/β-catenin pathways may play a role, but no clinical trials hav...

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Autores principales: Wang, Xiaoliang, Shojaie, Ali, Zhang, Yuzheng, Shelley, David, Lampe, Paul D., Levy, Lisa, Peters, Ulrike, Potter, John D., White, Emily, Lampe, Johanna W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5444835/
https://www.ncbi.nlm.nih.gov/pubmed/28542447
http://dx.doi.org/10.1371/journal.pone.0178444
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author Wang, Xiaoliang
Shojaie, Ali
Zhang, Yuzheng
Shelley, David
Lampe, Paul D.
Levy, Lisa
Peters, Ulrike
Potter, John D.
White, Emily
Lampe, Johanna W.
author_facet Wang, Xiaoliang
Shojaie, Ali
Zhang, Yuzheng
Shelley, David
Lampe, Paul D.
Levy, Lisa
Peters, Ulrike
Potter, John D.
White, Emily
Lampe, Johanna W.
author_sort Wang, Xiaoliang
collection PubMed
description Long-term use of aspirin is associated with lower risk of colorectal cancer and other cancers; however, the mechanism of chemopreventive effect of aspirin is not fully understood. Animal studies suggest that COX-2, NFκB signaling and Wnt/β-catenin pathways may play a role, but no clinical trials have systematically evaluated the biological response to aspirin in healthy humans. Using a high-density antibody array, we assessed the difference in plasma protein levels after 60 days of regular dose aspirin (325 mg/day) compared to placebo in a randomized double-blinded crossover trial of 44 healthy non-smoking men and women, aged 21–45 years. The plasma proteome was analyzed on an antibody microarray with ~3,300 full-length antibodies, printed in triplicate. Moderated paired t-tests were performed on individual antibodies, and gene-set analyses were performed based on KEGG and GO pathways. Among the 3,000 antibodies analyzed, statistically significant differences in plasma protein levels were observed for nine antibodies after adjusting for false discoveries (FDR adjusted p-value<0.1). The most significant protein was succinate dehydrogenase subunit C (SDHC), a key enzyme complex of the mitochondrial tricarboxylic acid (TCA) cycle. The other statistically significant proteins (NR2F1, MSI1, MYH1, FOXO1, KHDRBS3, NFKBIE, LYZ and IKZF1) are involved in multiple pathways, including DNA base-pair repair, inflammation and oncogenic pathways. None of the 258 KEGG and 1,139 GO pathways was found to be statistically significant after FDR adjustment. This study suggests several chemopreventive mechanisms of aspirin in humans, which have previously been reported to play a role in anti- or pro-carcinogenesis in cell systems; however, larger, confirmatory studies are needed.
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spelling pubmed-54448352017-06-12 Exploratory plasma proteomic analysis in a randomized crossover trial of aspirin among healthy men and women Wang, Xiaoliang Shojaie, Ali Zhang, Yuzheng Shelley, David Lampe, Paul D. Levy, Lisa Peters, Ulrike Potter, John D. White, Emily Lampe, Johanna W. PLoS One Research Article Long-term use of aspirin is associated with lower risk of colorectal cancer and other cancers; however, the mechanism of chemopreventive effect of aspirin is not fully understood. Animal studies suggest that COX-2, NFκB signaling and Wnt/β-catenin pathways may play a role, but no clinical trials have systematically evaluated the biological response to aspirin in healthy humans. Using a high-density antibody array, we assessed the difference in plasma protein levels after 60 days of regular dose aspirin (325 mg/day) compared to placebo in a randomized double-blinded crossover trial of 44 healthy non-smoking men and women, aged 21–45 years. The plasma proteome was analyzed on an antibody microarray with ~3,300 full-length antibodies, printed in triplicate. Moderated paired t-tests were performed on individual antibodies, and gene-set analyses were performed based on KEGG and GO pathways. Among the 3,000 antibodies analyzed, statistically significant differences in plasma protein levels were observed for nine antibodies after adjusting for false discoveries (FDR adjusted p-value<0.1). The most significant protein was succinate dehydrogenase subunit C (SDHC), a key enzyme complex of the mitochondrial tricarboxylic acid (TCA) cycle. The other statistically significant proteins (NR2F1, MSI1, MYH1, FOXO1, KHDRBS3, NFKBIE, LYZ and IKZF1) are involved in multiple pathways, including DNA base-pair repair, inflammation and oncogenic pathways. None of the 258 KEGG and 1,139 GO pathways was found to be statistically significant after FDR adjustment. This study suggests several chemopreventive mechanisms of aspirin in humans, which have previously been reported to play a role in anti- or pro-carcinogenesis in cell systems; however, larger, confirmatory studies are needed. Public Library of Science 2017-05-25 /pmc/articles/PMC5444835/ /pubmed/28542447 http://dx.doi.org/10.1371/journal.pone.0178444 Text en © 2017 Wang 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 (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Wang, Xiaoliang
Shojaie, Ali
Zhang, Yuzheng
Shelley, David
Lampe, Paul D.
Levy, Lisa
Peters, Ulrike
Potter, John D.
White, Emily
Lampe, Johanna W.
Exploratory plasma proteomic analysis in a randomized crossover trial of aspirin among healthy men and women
title Exploratory plasma proteomic analysis in a randomized crossover trial of aspirin among healthy men and women
title_full Exploratory plasma proteomic analysis in a randomized crossover trial of aspirin among healthy men and women
title_fullStr Exploratory plasma proteomic analysis in a randomized crossover trial of aspirin among healthy men and women
title_full_unstemmed Exploratory plasma proteomic analysis in a randomized crossover trial of aspirin among healthy men and women
title_short Exploratory plasma proteomic analysis in a randomized crossover trial of aspirin among healthy men and women
title_sort exploratory plasma proteomic analysis in a randomized crossover trial of aspirin among healthy men and women
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5444835/
https://www.ncbi.nlm.nih.gov/pubmed/28542447
http://dx.doi.org/10.1371/journal.pone.0178444
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