Differences in the early stage gene expression profiles of lung adenocarcinoma and lung squamous cell carcinoma.

Abstract

The discovery of lung carcinoma subtype-specific gene expression changes has the potential to elucidate the molecular differences and provide personalized therapeutic targets for these pathologies. The aim of the present study was to characterize the genetic profiles of the early stages (IA/IB) of two non-small cell lung cancer subtypes, adenocarcinoma (AD) and squamous cell carcinoma (SC). RNA-Seq gene expression data from The Cancer Genome Atlas was analyzed to compare the gene expression differences between AD and SC. The gene sets specific to each subtype were further analyzed to identify the enriched Gene Ontology terms, Kyoto Encyclopedia of Genes and Genomes pathways and biological functions. The results demonstrated that a unique set of genes (145 upregulated and 27 downregulated) was altered in AD, but not in SC; another set of genes (146 upregulated and 103 downregulated) was significantly altered in SC, but not in AD. Genes highly upregulated specifically in AD included albumin (1,732-fold), protein lin-28 homolog A, which is a positive regulator of cyclin-dependent kinase 2 (150-fold) and gastric lipase (81-fold). Genes highly upregulated specifically in SC included amelotin (618-fold), alcohol dehydrogenase 7 (57-fold), aclerosteosis (55-fold) and claudin-22 (54-fold). Several cancer/testis antigen family genes were notably upregulated in SC, but not in AD, whereas mucins were upregulated only in AD. Functional pathway analysis demonstrated that the dysregulation of genes associated with retinoid X receptors was common in AD and SC, genes associated with ‘lipid metabolism’ and ‘drug metabolism’ were dysregulated only in SC, whereas genes associated with ‘molecular transport’ and ‘cellular growth and proliferation’ were significantly enriched in AD specifically. These results reveal fundamental differences in the gene expression profiles of early-stage AD and SC. In addition, the present study identified molecular pathways that are uniquely associated with the pathogenesis of these subtypes.