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Article: Sex determining region Y-box 2 (SOX2) is a potential cell-lineage gene highly expressed in the pathogenesis of squamous cell carcinomas of the lung

TitleSex determining region Y-box 2 (SOX2) is a potential cell-lineage gene highly expressed in the pathogenesis of squamous cell carcinomas of the lung
Authors
Issue Date2010
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
Plos One, 2010, v. 5 n. 2 How to Cite?
Abstract
Background: Non-small cell lung cancer (NSCLC) represents the majority (85%) of lung cancers and is comprised mainly of adenocarcinomas and squamous cell carcinomas (SCCs). The sequential pathogenesis of lung adenocarcinomas and SCCs occurs through dissimilar phases as the former tumors typically arise in the lung periphery whereas the latter normally arise near the central airway. Methodology/Principal Findings:We assessed the expression of SOX2, an embryonic stem cell transcriptional factor that also plays important roles in the proliferation of basal tracheal cells and whose expression is restricted to the main and central airways and bronchioles of the developing and adult mouse lung, in NSCLC by various methodologies. Here, we found that SOX2 mRNA levels, from various published datasets, were significantly elevated in lung SCCs compared to adenocarcinomas (all p<0.001). Moreover, a previously characterized OCT4/SOX2/NANOG signature effectively separated lung SCCs from adenocarcinomas in two independent publicly available datasets which correlated with increased SOX2 mRNA in SCCs. Immunohistochemical analysis of various histological lung tissue specimens demonstrated marked nuclear SOX2 protein expression in all normal bronchial epithelia, alveolar bronchiolization structures and premalignant lesions in SCC development (hyperplasia, dysplasia and carcinoma in situ) and absence of expression in all normal alveoli and atypical adenomatous hyperplasias. Moreover, SOX2 protein expression was greatly higher in lung SCCs compared to adenocarcinomas following analyses in two independent large TMA sets (TMA set I, n = 287; TMA set II, n = 511 both p<0.001). Furthermore, amplification of SOX2 DNA was detected in 20% of lung SCCs tested (n = 40) and in none of the adenocarcinomas (n = 17). Conclusions/Significance: Our findings highlight a cell-lineage gene expression pattern for the stem cell transcriptional factor SOX2 in the pathogenesis of lung SCCs and suggest a differential activation of stem cell-related pathways between squamous cell carcinomas and adenocarcinomas of the lung. © 2010 Yuan et al.
Persistent Identifierhttp://hdl.handle.net/10722/146595
ISSN
2013 Impact Factor: 3.534
2013 SCImago Journal Rankings: 1.724
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Department of DefenseW81XWH-04-1-0142
W81XWH-07-1-03060
Specialized Program of Research Excellence in Lung CancerP50CA70907
National Cancer InstituteCA-16672
Funding Information:

This study was supported in part by grants from the Department of Defense (W81XWH-04-1-0142 and W81XWH-07-1-03060 to W. K. H., J. D. M., I. I. W.) and by the Specialized Program of Research Excellence in Lung Cancer Grant P50CA70907 (J. D. M., I. I. W.) and Cancer Center Support Grant CA-16672 from the National Cancer Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

References

 

DC FieldValueLanguage
dc.contributor.authorYuan, Pen_HK
dc.contributor.authorKadara, Hen_HK
dc.contributor.authorBehrens, Cen_HK
dc.contributor.authorTang, Xen_HK
dc.contributor.authorWoods, Den_HK
dc.contributor.authorSolis, LMen_HK
dc.contributor.authorHuang, Jen_HK
dc.contributor.authorSpinola, Men_HK
dc.contributor.authorDong, Wen_HK
dc.contributor.authorYin, Gen_HK
dc.contributor.authorFujimoto, Jen_HK
dc.contributor.authorKim, Een_HK
dc.contributor.authorXie, Yen_HK
dc.contributor.authorGirard, Len_HK
dc.contributor.authorMoran, Cen_HK
dc.contributor.authorHong, WKen_HK
dc.contributor.authorMinna, JDen_HK
dc.contributor.authorWistuba, IIen_HK
dc.date.accessioned2012-05-02T08:37:17Z-
dc.date.available2012-05-02T08:37:17Z-
dc.date.issued2010en_HK
dc.identifier.citationPlos One, 2010, v. 5 n. 2en_HK
dc.identifier.issn1932-6203en_HK
dc.identifier.urihttp://hdl.handle.net/10722/146595-
dc.description.abstractBackground: Non-small cell lung cancer (NSCLC) represents the majority (85%) of lung cancers and is comprised mainly of adenocarcinomas and squamous cell carcinomas (SCCs). The sequential pathogenesis of lung adenocarcinomas and SCCs occurs through dissimilar phases as the former tumors typically arise in the lung periphery whereas the latter normally arise near the central airway. Methodology/Principal Findings:We assessed the expression of SOX2, an embryonic stem cell transcriptional factor that also plays important roles in the proliferation of basal tracheal cells and whose expression is restricted to the main and central airways and bronchioles of the developing and adult mouse lung, in NSCLC by various methodologies. Here, we found that SOX2 mRNA levels, from various published datasets, were significantly elevated in lung SCCs compared to adenocarcinomas (all p<0.001). Moreover, a previously characterized OCT4/SOX2/NANOG signature effectively separated lung SCCs from adenocarcinomas in two independent publicly available datasets which correlated with increased SOX2 mRNA in SCCs. Immunohistochemical analysis of various histological lung tissue specimens demonstrated marked nuclear SOX2 protein expression in all normal bronchial epithelia, alveolar bronchiolization structures and premalignant lesions in SCC development (hyperplasia, dysplasia and carcinoma in situ) and absence of expression in all normal alveoli and atypical adenomatous hyperplasias. Moreover, SOX2 protein expression was greatly higher in lung SCCs compared to adenocarcinomas following analyses in two independent large TMA sets (TMA set I, n = 287; TMA set II, n = 511 both p<0.001). Furthermore, amplification of SOX2 DNA was detected in 20% of lung SCCs tested (n = 40) and in none of the adenocarcinomas (n = 17). Conclusions/Significance: Our findings highlight a cell-lineage gene expression pattern for the stem cell transcriptional factor SOX2 in the pathogenesis of lung SCCs and suggest a differential activation of stem cell-related pathways between squamous cell carcinomas and adenocarcinomas of the lung. © 2010 Yuan et al.en_HK
dc.languageengen_US
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.actionen_HK
dc.relation.ispartofPLoS ONEen_HK
dc.titleSex determining region Y-box 2 (SOX2) is a potential cell-lineage gene highly expressed in the pathogenesis of squamous cell carcinomas of the lungen_HK
dc.typeArticleen_HK
dc.identifier.emailYin, G: gyin@hku.hken_HK
dc.identifier.authorityYin, G=rp00831en_HK
dc.description.naturepublished_or_final_versionen_US
dc.identifier.doi10.1371/journal.pone.0009112en_HK
dc.identifier.pmid20161759-
dc.identifier.pmcidPMC2817751-
dc.identifier.scopuseid_2-s2.0-77949360656en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77949360656&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume5en_HK
dc.identifier.issue2en_HK
dc.identifier.isiWOS:000274442600010-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridYuan, P=35188367800en_HK
dc.identifier.scopusauthoridKadara, H=15044674000en_HK
dc.identifier.scopusauthoridBehrens, C=7005441177en_HK
dc.identifier.scopusauthoridTang, X=7404100928en_HK
dc.identifier.scopusauthoridWoods, D=7401876008en_HK
dc.identifier.scopusauthoridSolis, LM=24538012900en_HK
dc.identifier.scopusauthoridHuang, J=7407192095en_HK
dc.identifier.scopusauthoridSpinola, M=6602313869en_HK
dc.identifier.scopusauthoridDong, W=16063096500en_HK
dc.identifier.scopusauthoridYin, G=8725807500en_HK
dc.identifier.scopusauthoridFujimoto, J=35479278100en_HK
dc.identifier.scopusauthoridKim, E=34874986700en_HK
dc.identifier.scopusauthoridXie, Y=8960359100en_HK
dc.identifier.scopusauthoridGirard, L=7101715512en_HK
dc.identifier.scopusauthoridMoran, C=7202557877en_HK
dc.identifier.scopusauthoridHong, WK=35378571700en_HK
dc.identifier.scopusauthoridMinna, JD=35380041500en_HK
dc.identifier.scopusauthoridWistuba, II=35375776900en_HK
dc.identifier.citeulike9893521-

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