Abstract
BackgroundIncidence and mortality of lung cancer have dramatically decreased during the last decades, yet still approximately 160,000 deaths per year occurred in United States. Smoking intensity, duration, starting age, as well as environmental cofactors including air-pollution, showed strong association with major types of lung cancer. Lung squamous cell carcinoma is a subtype of non-small cell lung cancer, which represents 25% of the cases. Thus, exploring the molecular pathogenic mechanisms of lung squamous cell carcinoma plays crucial roles in lung cancer clinical diagnosis and therapy.ResultsIn this study, we performed integrative analyses on 299 comparative datasets of RNA-seq and methylation data, collected from 513 lung squamous cell carcinoma cases in The Cancer Genome Atlas. The data were divided into high and low smoking groups based on smoking intensity (Numbers of packs per year). We identified 1002 significantly up-regulated genes and 534 significantly down-regulated genes, and explored their cellular functions and signaling pathways by bioconductor packages GOseq and KEGG. Global methylation status was analyzed and visualized in circular plot by CIRCOS. RNA-and methylation data were correlatively analyzed, and 24 unique genes were identified, for further investigation of regional CpG sites’ interactive patterns by bioconductor package coMET. AIRE, PENK, and SLC6A3 were the top 3 genes in the high and low smoking groups with significant differences.ConclusionsGene functions and DNA methylation patterns of these 24 genes are important and useful in disclosing the differences of gene expression and methylation profiling caused by different smoking levels.
Highlights
Incidence and mortality of lung cancer have dramatically decreased during the last decades, yet still approximately 160,000 deaths per year occurred in United States
Numerous studies had focused on genomic characteristics of non-small-cell lung carcinoma (NSCLC), especially mutated genes found in lung cancer patients
We aimed to identify biomarker genes related to the smoking intensity in Lung squamous cell cancer (LSCC) patients, and performed the integrative analysis using dataset downloaded from The Cancer Genome Atlas (TCGA)
Summary
Incidence and mortality of lung cancer have dramatically decreased during the last decades, yet still approximately 160,000 deaths per year occurred in United States. Duration, starting age, as well as environmental cofactors including air-pollution, showed strong association with major types of lung cancer. Lung squamous cell cancer (LSCC) is the second common subtype of the latter, which represented almost 25% of overall lung cancer [10]. Numerous studies had focused on genomic characteristics of NSCLC (including LSCC), especially mutated genes found in lung cancer patients. Epidemiology studies showed that there was an increasing risk of developing lung cancer in cigarette amount dependent manner on both GSTM1 and CYP1A1 gene mutate patients [15]. The TCGA project conducted a more comprehensive study on the genomes and regulatory pathways of LSCC, and reported more mutated genes, such as CDKN2A, PTEN, PIK3CA, NFE2L2, KEAP1 and RB1 [20]. With appropriated bioinformatics analysis tools, these data would be revisited/reinvestigated in a more comprehensive perspective of gene differentiation and regulatory pathways, and for the purpose to identify significant biomarkers for diagnosis and treatment
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