Smoking accounts for almost 80–90% of lung cancer cases, which is also the most frequent cause of cancer-related deaths in humans. With over 60 carcinogens in tobacco smoke, cells dividing at the time of carcinogen exposure are at particular risk of neoplasia. The present study aimed to investigate global gene expression differences in lung adenocarcinoma (LUAD) tumour samples of current smokers and non-smokers, in an attempt to elucidate biological mechanisms underlying divergent smoking effects. Current and non-smoker tumour samples were analysed using bioinformatics tools, examining differences in molecular drivers of cancer initiation and progression, as well as evaluating the effect of smoking and sex on epithelial mesenchymal transition (EMT). As a result, we identified 1150 differentially expressed genes showing visible differences in the expression profiles between the smoking subgroups. The genes were primarily involved in cell cycle, DNA replication, DNA repair, VEGF, GnRH, ErbB and T cell receptor signalling pathways. Our results show that smoking clearly affected E2F transcriptional activity and DNA repair pathways including mismatch repair, base excision repair and homologous recombination. We observed that sex could modify the effects of PLA2G2A and PRG4 in LUAD tumour samples, whereas sex and smoking status might possibly have a biological effect on the EMT-related genes: HEY2, OLFM1, SFRP1 and STRAP. We also identified potential epigenetic changes smoking solely might have on EMT-related genes, which may serve as potential diagnostic and prognostic biomarkers for LUAD patients.

中文翻译：

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具有烟草暴露特征的肺腺癌转录组的差异表达。

吸烟占肺癌病例的近 80-90%，这也是人类癌症相关死亡的最常见原因。由于烟草烟雾中含有 60 多种致癌物质，在接触致癌物质时分裂的细胞特别容易发生肿瘤。本研究旨在调查当前吸烟者和非吸烟者的肺腺癌 (LUAD) 肿瘤样本中的全球基因表达差异，试图阐明不同吸烟影响的生物学机制。使用生物信息学工具分析当前和非吸烟者肿瘤样本，检查癌症发生和进展的分子驱动因素的差异，以及评估吸烟和性别对上皮间充质转化 (EMT) 的影响。其结果，我们鉴定了 1150 个差异表达的基因，这些基因在吸烟亚组之间的表达谱中显示出明显的差异。这些基因主要参与细胞周期、DNA 复制、DNA 修复、VEGF、GnRH、ErbB 和 T 细胞受体信号通路。我们的结果表明，吸烟明显影响 E2F 转录活性和 DNA 修复途径，包括错配修复、碱基切除修复和同源重组。我们观察到性别可以改变 碱基切除修复和同源重组。我们观察到性别可以改变 碱基切除修复和同源重组。我们观察到性别可以改变PLA2G2A和PRG4 LUAD肿瘤样本中，而性别，吸烟状况有可能会对EMT相关基因的生物学效应：HEY2，OLFM1，SFRP1和表带。我们还确定了仅吸烟可能对 EMT 相关基因产生的潜在表观遗传变化，这可能作为 LUAD 患者的潜在诊断和预后生物标志物。