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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
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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
 
AuthorsYuan, P3
Kadara, H3
Behrens, C3
Tang, X3
Woods, D3
Solis, LM3
Huang, J2
Spinola, M4
Dong, W3
Yin, G3
Fujimoto, J3
Kim, E3
Xie, Y4
Girard, L4
Moran, C3
Hong, WK3
Minna, JD4 1
Wistuba, II3
 
Issue Date2010
 
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
 
CitationPlos One, 2010, v. 5 n. 2 [How to Cite?]
DOI: http://dx.doi.org/10.1371/journal.pone.0009112
 
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.
 
ISSN1932-6203
2013 Impact Factor: 3.534
2013 SCImago Journal Rankings: 1.724
 
DOIhttp://dx.doi.org/10.1371/journal.pone.0009112
 
PubMed Central IDPMC2817751
 
ISI Accession Number IDWOS:000274442600010
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.

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorYuan, P
 
dc.contributor.authorKadara, H
 
dc.contributor.authorBehrens, C
 
dc.contributor.authorTang, X
 
dc.contributor.authorWoods, D
 
dc.contributor.authorSolis, LM
 
dc.contributor.authorHuang, J
 
dc.contributor.authorSpinola, M
 
dc.contributor.authorDong, W
 
dc.contributor.authorYin, G
 
dc.contributor.authorFujimoto, J
 
dc.contributor.authorKim, E
 
dc.contributor.authorXie, Y
 
dc.contributor.authorGirard, L
 
dc.contributor.authorMoran, C
 
dc.contributor.authorHong, WK
 
dc.contributor.authorMinna, JD
 
dc.contributor.authorWistuba, II
 
dc.date.accessioned2012-05-02T08:37:17Z
 
dc.date.available2012-05-02T08:37:17Z
 
dc.date.issued2010
 
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.
 
dc.description.naturepublished_or_final_version
 
dc.identifier.citationPlos One, 2010, v. 5 n. 2 [How to Cite?]
DOI: http://dx.doi.org/10.1371/journal.pone.0009112
 
dc.identifier.citeulike9893521
 
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pone.0009112
 
dc.identifier.isiWOS:000274442600010
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.

 
dc.identifier.issn1932-6203
2013 Impact Factor: 3.534
2013 SCImago Journal Rankings: 1.724
 
dc.identifier.issue2
 
dc.identifier.pmcidPMC2817751
 
dc.identifier.pmid20161759
 
dc.identifier.scopuseid_2-s2.0-77949360656
 
dc.identifier.urihttp://hdl.handle.net/10722/146595
 
dc.identifier.volume5
 
dc.languageeng
 
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
 
dc.publisher.placeUnited States
 
dc.relation.ispartofPLoS ONE
 
dc.relation.referencesReferences in Scopus
 
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 lung
 
dc.typeArticle
 
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Author Affiliations
  1. UT Southwestern Medical School
  2. David Geffen School of Medicine at UCLA
  3. University of Texas M. D. Anderson Cancer Center
  4. UT Southwestern Medical Center