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
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ea6e02b999b9408bb1b3948e51c13215
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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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Meta-Analysis illustrates possible role of lipopolysaccharide (LPS)-induced tissue injury in nasopharyngeal carcinoma (NPC) pathogenesis.

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