Sex Determining Region Y-Box 2 SOX2 Is a Potential Cell-Lineage Gene Highly Expressed in the Pathogenesis of Squamous Cell Carcinomas of the LungReport as inadecuate




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 - Download this document for free, or read online. Document in PDF available to download.

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.



Author: Ping Yuan , Humam Kadara , Carmen Behrens, Ximing Tang, Denise Woods, Luisa M. Solis, Jiaoti Huang, Monica Spinola, Wenli Dong, G

Source: http://plos.srce.hr/



DOWNLOAD PDF




Related documents