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Abstract. Cigarette smoking is the leading risk factor for lung cancer, which accounts for the highest number of cancer-related mortalities worldwide in men and women. Individuals with a history of smoking are 15-30 times more likely to develop lung cancer compared with those who do not smoke. However, our understanding of the underlying molecular mechanisms that contribute to lung tumorigenesis in smokers versus non-smokers remains incomplete. In order to investigate such mechanisms, the present study aimed to systemically interrogate microarray datasets from tumor biopsies and matching normal tissues from stage I and II lung adenocarcinoma patients who had never smoked or were current smokers. The gene expression analysis identified 422 (99 upregulated and 323 downregulated) and 534 (174 upregulated and 360 downregulated) differentially-expressed genes from the never-smokers and current smokers, respectively, and the two groups shared 277 genes that exhibited similar trends of alteration. These genes encode regulators that are involved in a variety of cellular functions, including collagen metabolism and homeostasis of caveolae plasma membranes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes characterization indicated that biological pathways, including extracellular matrix-receptor interaction and cell migration and proliferation, were all affected in the lung cancer patients regardless of the smoking status. However, smoking induced a unique gene expression pattern characterized by upregulation of cell cycle regulators (CDK1, CCNB1 and CDC20), as well as significantly affected biological networks, including p53 signaling pathways. Taken together, these findings suggest novel mechanistic insights, and provide an improved understanding of the smoking-induced molecular alterations that contribute to the pathogenesis of lung adenocarcinoma.

Background Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease. Current gold standard criteria, pulmonary function tests (PFTs) may result in underdiagnosis of potential COPD patients. Therefore, we hypothesize that the combination of high-resolution computed tomography (HRCT) and clinical basic characteristics will enable the identification of more COPD patients. Methods A total of 284 patients with respiratory symptoms who were current or former smokers were included in the study, and were further divided into 5 groups of GOLD grade I–IV and non-COPD according to PFTs. All patients underwent inspiratory HRCT scanning and low attenuation area (LAA) was measured. Then they were divided into seven visual subtypes according to the Fleischner Society classification system. Non-parametric tests were used for exploring differences in basic characteristics and PFTs between different groups of enrolled patients and visual subtypes. Binary logistic regression was to find the influencing factors that affected the patients’ outcome (non-COPD vs GOLD I-IV). The area under the receiver operating characteristic curve (AUC-ROC) was to explore the diagnostic efficacy of LAA, visual subtypes, and combined basic characteristics related to COPD for COPD diagnosis. Finally, based on the cut-off values of ROC analysis, exploring HRCT features in patients who do not meet the diagnostic criteria but clinically suspected COPD. Results With the worsening severity of COPD, the visual subtypes gradually progressed (p < 0.01). There was a significant difference in LAA between GOLD II–IV and non-COPD (p < 0.0001). The diagnostic efficacy of LAA, visual subtypes, and LAA combined with visual subtypes for COPD were 0.742, 0.682 and 0.730 respectively. The diagnostic efficacy increased to 0.923–0.943 when basic characteristics were added (all p < 0.001). Based on the cut-off value of ROC analysis, LAA greater than 5.6, worsening of visual subtypes, combined with positive basic characteristics can help identify some potential COPD patients. Conclusion The heterogeneous phenotype of COPD requires a combination of multiple evaluation methods. The diagnostic efficacy of combining LAA, visual subtypes, and basic characteristics achieves good consistency with current diagnostic criteria.

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