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

Ping Yuan, Humam Kadara, Carmen Behrens, Ximing Tang, Denise Woods, Luisa M. Solis, Jiaoti Huang, Monica Spinola, Wenli Dong, Guosheng Yin, Junya Fujimoto, Edward Kim, Yang Xie, Luc Girard, Cesar Moran, Waun Ki Hong, John D. Minna, Ignacio I. Wistuba

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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.

Original languageEnglish (US)
Article numbere9112
JournalPLoS One
Volume5
Issue number2
DOIs
StatePublished - Feb 9 2010

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squamous cell carcinoma
Cell Lineage
Squamous Cell Carcinoma
pathogenesis
Genes
lungs
adenocarcinoma
Lung
gender
Adenocarcinoma
genes
cells
lung neoplasms
Stem cells
Stem Cell Factor
hyperplasia
Non-Small Cell Lung Carcinoma
Hyperplasia
stem cells
transcription factors

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

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. / Yuan, Ping; Kadara, Humam; Behrens, Carmen; Tang, Ximing; Woods, Denise; Solis, Luisa M.; Huang, Jiaoti; Spinola, Monica; Dong, Wenli; Yin, Guosheng; Fujimoto, Junya; Kim, Edward; Xie, Yang; Girard, Luc; Moran, Cesar; Hong, Waun Ki; Minna, John D.; Wistuba, Ignacio I.

In: PLoS One, Vol. 5, No. 2, e9112, 09.02.2010.

Research output: Contribution to journalArticle

Yuan, P, Kadara, H, Behrens, C, Tang, X, Woods, D, Solis, LM, Huang, J, Spinola, M, Dong, W, Yin, G, Fujimoto, J, Kim, E, Xie, Y, Girard, L, Moran, C, Hong, WK, Minna, JD & Wistuba, II 2010, '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', PLoS One, vol. 5, no. 2, e9112. https://doi.org/10.1371/journal.pone.0009112
Yuan, Ping ; Kadara, Humam ; Behrens, Carmen ; Tang, Ximing ; Woods, Denise ; Solis, Luisa M. ; Huang, Jiaoti ; Spinola, Monica ; Dong, Wenli ; Yin, Guosheng ; Fujimoto, Junya ; Kim, Edward ; Xie, Yang ; Girard, Luc ; Moran, Cesar ; Hong, Waun Ki ; Minna, John D. ; Wistuba, Ignacio I. / 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. In: PLoS One. 2010 ; Vol. 5, No. 2.
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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.",
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AU - Yuan, Ping

AU - Kadara, Humam

AU - Behrens, Carmen

AU - Tang, Ximing

AU - Woods, Denise

AU - Solis, Luisa M.

AU - Huang, Jiaoti

AU - Spinola, Monica

AU - Dong, Wenli

AU - Yin, Guosheng

AU - Fujimoto, Junya

AU - Kim, Edward

AU - Xie, Yang

AU - Girard, Luc

AU - Moran, Cesar

AU - Hong, Waun Ki

AU - Minna, John D.

AU - Wistuba, Ignacio I.

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N2 - 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.

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