RNA-seq analysis of lung adenocarcinomas reveals different gene expression profiles between smoking and nonsmoking patients.

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Exploring the gene expression profile and identifying genes that are shared or vary between smokers and nonsmokers with lung adenocarcinoma will provide insights into the etiology of this complex cancer. We obtained RNA-seq data from paired normal and tumor tissues from 34 nonsmoking and 34 smoking patients with lung adenocarcinoma (GEO: GSE40419). R Bioconductor, edgeR, was adopted to conduct differential gene expression analysis between paired normal and tumor tissues. A generalized linear model was applied to identify genes that were differentially expressed in nonsmoker and smoker patients as well as genes that varied between these two groups. We identified 2273 genes that showed differential expression with FDR < 0.05 and |logFC| >1 in nonsmoker tumor versus normal tissues; 3030 genes in the smoking group; and 1967 genes were common to both groups. Sixty-eight and 70% of the identified genes were downregulated in nonsmoking and smoking groups, respectively. The 20 genes such as SPP1, SPINK1, and FAM83A with largest fold changes in smokers also showed similar large and highly significant fold changes in nonsmokers and vice versa, showing commonalities in expression changes for adenocarcinomas in both smokers and nonsmokers for these genes. We also identified 175 genes that were significantly differently expressed between tumor samples from nonsmoker and smoker patients. Gene expression profile varied substantially between smoker and nonsmoker patients with lung adenocarcinoma. Smoking patients overall showed far more complicated disease mechanism and have more dysregulation in their gene expression profiles. Our study reveals pathogenetic differences in smoking and nonsmoking patients with lung adenocarcinoma from transcriptome analysis. We provided a list of candidate genes for further study for disease detection and treatment in both smoking and nonsmoking patients with lung adenocarcinoma.", "claims": [{"id": "claim-target-result", "statement": "The study used R Bioconductor edgeR with a generalized linear model to analyze differential gene expression in paired normal and tumor RNA-seq data from 34 nonsmoking and 34 smoking patients with lung adenocarcinoma obtained from GEO accession GSE40419.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:26081616", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "We obtained RNA-seq data from paired normal and tumor tissues from 34 nonsmoking and 34 smoking patients with lung adenocarcinoma (GEO: GSE40419)."}, {"asset": "source:pmid:26081616", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "R Bioconductor, edgeR, was adopted to conduct differential gene expression analysis between paired normal and tumor tissues."}, {"asset": "source:pmid:26081616", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "A generalized linear model was applied to identify genes that were differentially expressed in nonsmoker and smoker patients as well as genes that varied between these two groups."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The study used R Bioconductor edgeR with a generalized linear model to analyze differential gene expression in paired normal and tumor RNA-seq data from 34 nonsmoking and 34 smoking patients with lung adenocarcinoma obtained from GEO accession GSE40419.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:26081616"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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