Meta-Analysis illustrates possible role of lipopolysaccharide (LPS)-induced tissue injury in nasopharyngeal carcinoma (NPC) pathogenesis.

<h4>Background</h4>Nasopharyngeal carcinoma (NPC) is a cancer of epithelial origin with a high incidence in certain populations. While NPC has a high remission rate with concomitant chemoradiation, recurrences are frequent, and the downstream morbidity of treatment is significant. Thus,...

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Autores principales: David Z Allen, Jihad Aljabban, Dustin Silverman, Sean McDermott, Ross A Wanner, Michael Rohr, Dexter Hadley, Maryam Panahiazar
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Publicado: Public Library of Science (PLoS) 2021
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spelling oai:doaj.org-article:ea6e02b999b9408bb1b3948e51c132152021-12-02T20:16:57ZMeta-Analysis illustrates possible role of lipopolysaccharide (LPS)-induced tissue injury in nasopharyngeal carcinoma (NPC) pathogenesis.1932-620310.1371/journal.pone.0258187https://doaj.org/article/ea6e02b999b9408bb1b3948e51c132152021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0258187https://doaj.org/toc/1932-6203<h4>Background</h4>Nasopharyngeal carcinoma (NPC) is a cancer of epithelial origin with a high incidence in certain populations. While NPC has a high remission rate with concomitant chemoradiation, recurrences are frequent, and the downstream morbidity of treatment is significant. Thus, it is imperative to find alternative therapies.<h4>Methods</h4>We employed a Search Tag Analyze Resource (STARGEO) platform to conduct a meta-analysis using the National Center for Biotechnology's (NCBI) Gene Expression Omnibus (GEO) to define NPC pathogenesis. We identified 111 tumor samples and 43 healthy nasopharyngeal epithelium samples from NPC public patient data. We analyzed associated signatures in Ingenuity Pathway Analysis (IPA), restricting genes that showed statistical significance (p<0.05) and an absolute experimental log ratio greater than 0.15 between disease and control samples.<h4>Results</h4>Our meta-analysis identified activation of lipopolysaccharide (LPS)-induced tissue injury in NPC tissue. Additionally, interleukin-1 (IL-1) and SB203580 were the top upstream regulators. Tumorigenesis-related genes such as homeobox A10 (HOXA10) and prostaglandin-endoperoxide synthase 2 (PTGS2 or COX-2) as well as those associated with extracellular matrix degradation, such as matrix metalloproteinases 1 and 3 (MMP-1, MMP-3) were also upregulated. Decreased expression of genes that encode proteins associated with maintaining healthy nasal respiratory epithelium structural integrity, including sentan-cilia apical structure protein (SNTN) and lactotransferrin (LTF) was documented. Importantly, we found that etanercept inhibits targets upregulated in NPC and LPS induction, such as MMP-1, PTGS2, and possibly MMP-3.<h4>Conclusions</h4>Our analysis illustrates that nasal epithelial barrier dysregulation and maladaptive immune responses are key components of NPC pathogenesis along with LPS-induced tissue damage.David Z AllenJihad AljabbanDustin SilvermanSean McDermottRoss A WannerMichael RohrDexter HadleyMaryam PanahiazarPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 10, p e0258187 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
David Z Allen
Jihad Aljabban
Dustin Silverman
Sean McDermott
Ross A Wanner
Michael Rohr
Dexter Hadley
Maryam Panahiazar
Meta-Analysis illustrates possible role of lipopolysaccharide (LPS)-induced tissue injury in nasopharyngeal carcinoma (NPC) pathogenesis.
description <h4>Background</h4>Nasopharyngeal carcinoma (NPC) is a cancer of epithelial origin with a high incidence in certain populations. While NPC has a high remission rate with concomitant chemoradiation, recurrences are frequent, and the downstream morbidity of treatment is significant. Thus, it is imperative to find alternative therapies.<h4>Methods</h4>We employed a Search Tag Analyze Resource (STARGEO) platform to conduct a meta-analysis using the National Center for Biotechnology's (NCBI) Gene Expression Omnibus (GEO) to define NPC pathogenesis. We identified 111 tumor samples and 43 healthy nasopharyngeal epithelium samples from NPC public patient data. We analyzed associated signatures in Ingenuity Pathway Analysis (IPA), restricting genes that showed statistical significance (p<0.05) and an absolute experimental log ratio greater than 0.15 between disease and control samples.<h4>Results</h4>Our meta-analysis identified activation of lipopolysaccharide (LPS)-induced tissue injury in NPC tissue. Additionally, interleukin-1 (IL-1) and SB203580 were the top upstream regulators. Tumorigenesis-related genes such as homeobox A10 (HOXA10) and prostaglandin-endoperoxide synthase 2 (PTGS2 or COX-2) as well as those associated with extracellular matrix degradation, such as matrix metalloproteinases 1 and 3 (MMP-1, MMP-3) were also upregulated. Decreased expression of genes that encode proteins associated with maintaining healthy nasal respiratory epithelium structural integrity, including sentan-cilia apical structure protein (SNTN) and lactotransferrin (LTF) was documented. Importantly, we found that etanercept inhibits targets upregulated in NPC and LPS induction, such as MMP-1, PTGS2, and possibly MMP-3.<h4>Conclusions</h4>Our analysis illustrates that nasal epithelial barrier dysregulation and maladaptive immune responses are key components of NPC pathogenesis along with LPS-induced tissue damage.
format article
author David Z Allen
Jihad Aljabban
Dustin Silverman
Sean McDermott
Ross A Wanner
Michael Rohr
Dexter Hadley
Maryam Panahiazar
author_facet David Z Allen
Jihad Aljabban
Dustin Silverman
Sean McDermott
Ross A Wanner
Michael Rohr
Dexter Hadley
Maryam Panahiazar
author_sort David Z Allen
title Meta-Analysis illustrates possible role of lipopolysaccharide (LPS)-induced tissue injury in nasopharyngeal carcinoma (NPC) pathogenesis.
title_short Meta-Analysis illustrates possible role of lipopolysaccharide (LPS)-induced tissue injury in nasopharyngeal carcinoma (NPC) pathogenesis.
title_full Meta-Analysis illustrates possible role of lipopolysaccharide (LPS)-induced tissue injury in nasopharyngeal carcinoma (NPC) pathogenesis.
title_fullStr Meta-Analysis illustrates possible role of lipopolysaccharide (LPS)-induced tissue injury in nasopharyngeal carcinoma (NPC) pathogenesis.
title_full_unstemmed Meta-Analysis illustrates possible role of lipopolysaccharide (LPS)-induced tissue injury in nasopharyngeal carcinoma (NPC) pathogenesis.
title_sort meta-analysis illustrates possible role of lipopolysaccharide (lps)-induced tissue injury in nasopharyngeal carcinoma (npc) pathogenesis.
publisher Public Library of Science (PLoS)
publishDate 2021
url https://doaj.org/article/ea6e02b999b9408bb1b3948e51c13215
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