PDF(Pubmed)
Abstract：
Cigarette smoke initiates an inflammatory response that has aftermath long after quitting. We segregated former smokers, according to their lung function and their co-founding diseases, in 3 groups: Cancer, Emphysema and COPD. Then we searched for outlier genes in intersections of Venn diagrams where we identified 6 subsets and 23 genes that may be responsible for disease outcome. Genes expressed in the cancer patients with or without emphysema (PPA subset) were BHLH, FPRL2, CD49D, DEADH, NRs4A3, MBLL, GNS, BE675435, ISGF-3, and FLJ23462. Patients with emphysema as co-founding disease, with or without cancer (APP), had only ANXA2 in common. Genes expressed only in non-cancer patients (AAP subset) of COPD group were IL-1A, SOX13, RPP38; TBXA2R, NPEPL1, CFLAR, TFEB, PRKCBP1, IGF1R, DDX11, and KCNAB1. HIV-1Rev was the gene expressed in cancer patients with emphysema (APA subset). Then, we also looked at out-layers genes significantly expressed in all patients (PPP subset with 5066 genes), the down-regulated in Emphysema were MMP9, PLUNC, CEACAM5, and NR4A1 while the up-regulated were F2R, COL15A1, PDE4C, and BGN. We chose genes and checked them at the protein level on immune cells, this showed that neutrophils from Cancer group had increased expression of CD49d, and their total number was also increased in bronchial-alveolar lavage (154%). Macrophages in the lung of patients with emphysema were associated with a significant increase of adhesion molecule CD58 and to significant CD95 decrease, indicating they do not die. Besides, macrophages downregulated MMP9 in the lung compared to blood macrophages. Overall, we find that cancer progression requires a stickier and greater number of neutrophils in the lung while emphysema requires stickier and longevous macrophages to lead matrix destruction, and together with higher expression of SOX13 and RPP38, may promote autoimmunity. We also identified two genes, ANXA2 and HIV1-rev, that may be a pivot between cancer and emphysema outcome of inflammation.
摘要：
香烟烟雾会引发炎症反应，这种反应在戒烟后很久就会产生后果。我们隔离了以前的吸烟者，根据他们的肺功能和共同创立的疾病，分为3组：癌症，肺气肿和COPD。然后，我们在维恩图的交叉点中搜索了离群基因，其中我们确定了可能导致疾病结果的6个子集和23个基因。在有或没有肺气肿的癌症患者（PPA亚群）中表达的基因是BHLH，FPRL2,CD49D,死亡,NRs4A3,MBLL,GNS,BE675435、ISGF-3和FLJ23462。肺气肿作为共同疾病的患者，有或没有癌症（APP），只有ANXA2是共同的。仅在COPD组的非癌症患者（AAP亚群）中表达的基因是IL-1A，SOX13,RPP38;TBXA2R,NPEPL1,CFLAR,TFEB,PRKCBP1,IGF1R,DDX11和KCNAB1。HIV-1Rev是在患有肺气肿的癌症患者(APA亚群)中表达的基因。然后，我们还研究了在所有患者中显著表达的外层基因（PPP子集有5066个基因），肺气肿中下调的是MMP9，PLUNC，CEACAM5和NR4A1上调的是F2R，COL15A1,PDE4C,和BGN。我们选择了基因，并在免疫细胞的蛋白质水平上检查了它们，这表明来自癌症组的中性粒细胞CD49d的表达增加，在支气管肺泡灌洗中，它们的总数也增加了（154％）。肺气肿患者的肺巨噬细胞与粘附分子CD58的显着增加和CD95的显着减少有关，表明他们不会死。此外,与血液巨噬细胞相比，巨噬细胞下调肺中的MMP9。总的来说,我们发现，癌症的进展需要一个粘性和更多的中性粒细胞在肺中，而肺气肿需要粘性和长期巨噬细胞导致基质破坏，与SOX13和RPP38的较高表达一起，可能促进自身免疫。我们还鉴定了两个基因,ANXA2和HIV1-rev，这可能是癌症和肺气肿炎症结果之间的枢纽。
