Ercetin Evrim, Richtmann Sarah, Delgado Beatriz Martinez, Gomez-Mariano Gema, Wrenger Sabine, Korenbaum Elena, Liu Bin, DeLuca David, Kühnel Mark P, Jonigk Danny, Yuskaeva Kadriya, Warth Arne, Muley Thomas, Winter Hauke, Meister Michael, Welte Tobias, Janciauskiene Sabina, Schneider Marc A
Department of Respiratory Medicine, Hannover Medical School, 30625 Hannover, Germany.
Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), 30625 Hannover, Germany.
Cancers (Basel). 2019 Sep 4;11(9):1306. doi: 10.3390/cancers11091306.
High expression of gene encoding acute phase protein, alpha1-antitrypsin (AAT), is associated with various tumors. We sought to examine the significance of and AAT protein in non-small-cell lung cancer (NSCLC) patients and NSCLC cell lines. Tumor and adjacent non-tumor lung tissues and serum samples from 351 NSCLC patients were analyzed for expression and AAT protein levels. We also studied the impact of expression and AAT protein on H1975 and H661 cell behavior, . Lower expression in tumor but higher in adjacent non-tumor lung tissues ( = 351, = 0.016) as well as higher serum levels of AAT protein ( = 170, = 0.033) were associated with worse survival rates. Specifically, in NSCLC stage III patients, higher blood AAT levels (>2.66 mg/mL) correlated with a poor survival ( = 0.002). Intriguingly, levels of serum AAT do not correlate with levels of C-reactive protein, neutrophils-to-leukocyte ratio, and do not correlate with expression or AAT staining in the tumor tissue. Additional experiments revealed that external AAT and/or overexpressed gene significantly improve cancer cell migration, colony formation and resistance to apoptosis. gene and AAT protein play an active role in the pathogenesis of lung cancer and not just reflect inflammatory reaction related to cancer development.
编码急性期蛋白α1-抗胰蛋白酶（AAT）的基因高表达与多种肿瘤相关。我们试图研究[基因名称]和AAT蛋白在非小细胞肺癌（NSCLC）患者及NSCLC细胞系中的意义。对351例NSCLC患者的肿瘤及邻近非肿瘤肺组织和血清样本进行了[基因名称]表达及AAT蛋白水平分析。我们还研究了[基因名称]表达和AAT蛋白对H1975和H661细胞行为的影响。肿瘤组织中[基因名称]表达较低而邻近非肿瘤肺组织中较高（n = 351，P = 0.016），以及血清中AAT蛋白水平较高（n = 170，P = 0.033）均与较差的生存率相关。具体而言，在NSCLC III期患者中，较高的血液AAT水平（>2.66 mg/mL）与较差的生存率相关（P = 0.002）。有趣的是，血清AAT水平与C反应蛋白水平、中性粒细胞与白细胞比值均无相关性，且与肿瘤组织中的[基因名称]表达或AAT染色也无相关性。进一步实验表明，外源性AAT和/或过表达的[基因名称]显著促进癌细胞迁移、集落形成及抗凋亡能力。[基因名称]和AAT蛋白在肺癌发病机制中发挥积极作用，而不仅仅反映与癌症发展相关的炎症反应。
