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

• Published in: PloS one Vol. 5; no. 2; p. e9112
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 09.02.2010; Public Library of Science (PLoS)
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Alveoli; Analysis; Biopsy; Cancer; Cancer genetics; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Cell activation; Cell Lineage - genetics; Cell proliferation; Cluster Analysis; Data mining; Datasets; Deoxyribonucleic acid; DNA; Drosophila; Dysplasia; Embryonic stem cells; Epigenetics; Esophagus; Female; Fibroblasts; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genes; Growth factors; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Humans; Hyperplasia; Immunohistochemistry; Insects; Lesions; Lung - chemistry; Lung - metabolism; Lung - pathology; Lung cancer; Lung carcinoma; Lung diseases; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Male; Morphogenesis; Nanog Homeobox Protein; Non-small cell lung cancer; Non-small cell lung carcinoma; Oct-4 protein; Octamer Transcription Factor-3 - genetics; Octamer Transcription Factor-3 - metabolism; Oligonucleotide Array Sequence Analysis; Oncology; Oncology/Lung Cancer; Pathogenesis; Pathology; Pathology/Molecular Pathology; Precancerous Conditions - genetics; Precancerous Conditions - metabolism; Precancerous Conditions - pathology; Respiratory tract; Reverse Transcriptase Polymerase Chain Reaction; RNA; Rodents; Sox2 protein; SOXB1 Transcription Factors - genetics; SOXB1 Transcription Factors - metabolism; Squamous cell carcinoma; Stem cells; Tissue Array Analysis; Transcription (Genetics); Tumors; Los Angeles California; California; United States > US; Texas
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0009112

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. 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). 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.