title: 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.
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.
  
  
  RESULTS
  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
  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.
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Ping
authors.initials: P
authors.lastname: Yuan
authors.forename: Humam
authors.initials: H
authors.lastname: Kadara
authors.forename: Carmen
authors.initials: C
authors.lastname: Behrens
authors.forename: Ximing
authors.initials: X
authors.lastname: Tang
authors.forename: Denise
authors.initials: D
authors.lastname: Woods
authors.forename: Luisa M
authors.initials: LM
authors.lastname: Solis
authors.forename: Jiaoti
authors.initials: J
authors.lastname: Huang
authors.forename: Monica
authors.initials: M
authors.lastname: Spinola
authors.forename: Wenli
authors.initials: W
authors.lastname: Dong
authors.forename: Guosheng
authors.initials: G
authors.lastname: Yin
authors.forename: Junya
authors.initials: J
authors.lastname: Fujimoto
authors.forename: Edward
authors.initials: E
authors.lastname: Kim
authors.forename: Yang
authors.initials: Y
authors.lastname: Xie
authors.forename: Luc
authors.initials: L
authors.lastname: Girard
authors.forename: Cesar
authors.initials: C
authors.lastname: Moran
authors.forename: Waun Ki
authors.initials: WK
authors.lastname: Hong
authors.forename: John D
authors.initials: JD
authors.lastname: Minna
authors.forename: Ignacio I
authors.initials: II
authors.lastname: Wistuba
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019070:Cell Lineage / Q000235:genetics; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011230:Precancerous Conditions / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism*; D046888:Tissue Array Analysis
chemical_list: D018398:Homeodomain Proteins; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors