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.

Comprehensive micro-scaled proteome and phosphoproteome characterization of archived retrospective cancer repositories

“…In SCC we could confirm apolipoprotein 1 (APOA1) which has previously been described as inversely correlated with the risk of lung cancer 26 . Interestingly, the paper by Venugopal et al 23 showed fibrinogen alpha (FGA) to be overexpressed in ADC, in our dataset, however, it was found with higher expression levels in SCC. In addition, we were able to quantify several proteins that might be of interest as potential future markers for lung ADC, such as mucin-5AC (MUC5AC), another mucin that has been linked to ALK-positive lung ADC 27 , or carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6), a glycoprotein that is involved in cell invasion and metastasis and has been shown to have higher expression levels in ADC compared to SCC via IHC 28 .…”

“…2A ). With this dataset, we could confirm several markers on a protein level that had previously been shown on RNA level 23 , such as mucin-5B (MUC5B), a glycoprotein that is secreted in the lung and is associated with poor prognosis in ADC 24 , kininogen 1 (KNG1), and serum transthyretin (TTR), which has been shown to be associated with poor outcome 25 . In SCC we could confirm apolipoprotein 1 (APOA1) which has previously been described as inversely correlated with the risk of lung cancer 26 .…”

Comprehensive micro-scaled proteome and phosphoproteome characterization of archived retrospective cancer repositories

“…In SCC we could confirm apolipoprotein 1 (APOA1) which has previously been described as inversely correlated with the risk of lung cancer 26 . Interestingly, the paper by Venugopal et al 23 showed fibrinogen alpha (FGA) to be overexpressed in ADC, in our dataset, however, it was found with higher expression levels in SCC. In addition, we were able to quantify several proteins that might be of interest as potential future markers for lung ADC, such as mucin-5AC (MUC5AC), another mucin that has been linked to ALK-positive lung ADC 27 , or carcinoembryonic antigen-related cell adhesion molecule 6 (CEA-CAM6), a glycoprotein that is involved in cell invasion and metastasis and has been shown to have higher expression levels in ADC compared to SCC via IHC 28 .…”

The expression of Lin28 in gastric cancer cells treated with an anticancer bioactive peptide combined with oxaliplatin in vitro and in vivo

“…However, the results of this experiment show that the effect of ACBP is different at the protein level compared with the mRNA level, and further research on the relevant signaling process is needed. GES-1 is a tumorigenic [12], immortalized human gastric mucosal epithelial cell line, and Lin28 is highly expressed in growing and developing GES-1 cells; it exhibits high expression in multiple tumor cell lines [33] and comparatively low expression in human gastric mucosal cells. The results of this study indicated that OXA, ACBP and the combination downregulated Lin28 gene expression, but the Lin28 protein expression level was not measured in GES-1 cells due to its low expression in these cells.…”