Pulmonology Department, Lung Cancer and Muscle Research Group, Hospital del Mar-IMIM, Parc de Salut Mar, Health and Experimental Sciences Department (CEXS), Universitat Pompeu Fabra (UPF), Parc de Recerca Biomèdica de Barcelona (PRBB), C/ Dr. Aiguader, 88, E-08003 Barcelona, Spain.
2Centro de Investigación en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Barcelona, Spain.
Clin Epigenetics. 2018 Jan 16;10:7. doi: 10.1186/s13148-017-0437-0. eCollection 2018.
Chronic lung diseases such as chronic obstructive pulmonary disease (COPD) and epigenetic events underlie lung cancer (LC) development. The study objective was that lung tumor expression levels of specific microRNAs and their downstream biomarkers may be differentially regulated in patients with and without COPD.
In lung specimens (tumor and non-tumor), microRNAs known to be involved in lung tumorigenesis (miR-21, miR-200b, miR-126, miR-451, miR-210, miR-let7c, miR-30a-30p, miR-155 and miR-let7a, qRT-PCR), DNA methylation, and downstream biomarkers were determined (qRT-PCR and immunoblotting) in 40 patients with LC (prospective study, subdivided into LC-COPD and LC, = 20/group).
Expression of miR-21, miR-200b, miR-210, and miR-let7c and DNA methylation were greater in lung tumor specimens of LC-COPD than of LC patients. Expression of downstream markers , , , , , , , , , and together with were selectively downregulated in tumor samples of LC-COPD patients. In these patients, tumor expression of miR-126 and miR-451 and that of the biomarkers , , , , , and were reduced.
Biomarkers of mechanisms involved in tumor growth, angiogenesis, migration, and apoptosis were differentially expressed in tumors of patients with underlying respiratory disease. These findings shed light into the underlying biology of the reported greater risk to develop LC seen in patients with chronic respiratory conditions. The presence of an underlying respiratory disease should be identified in all patients with LC as the differential biological profile may help determine tumor progression and the therapeutic response. Additionally, epigenetic events offer a niche for pharmacological therapeutic targets.
慢性肺部疾病（如慢性阻塞性肺疾病，COPD）和表观遗传事件是肺癌（LC）发展的基础。本研究的目的是，在患有和不患有 COPD 的患者中，肺部肿瘤中特定 microRNA 及其下游生物标志物的表达水平可能存在差异调节。
在肺标本（肿瘤和非肿瘤）中，测定了已知与肺肿瘤发生相关的 microRNAs（miR-21、miR-200b、miR-126、miR-451、miR-210、miR-let7c、miR-30a-30p、miR-155 和 miR-let7a）、DNA 甲基化和下游生物标志物（qRT-PCR 和免疫印迹）的表达水平，纳入 40 名 LC 患者（前瞻性研究，分为 LC-COPD 和 LC 患者，每组 20 名）。
与 LC 患者相比，LC-COPD 患者的肺肿瘤标本中 miR-21、miR-200b、miR-210 和 miR-let7c 的表达以及 DNA 甲基化程度更高。下游标志物 、 、 、 、 、 、 、 、 和 ，连同 ，在 LC-COPD 患者的肿瘤样本中选择性下调。在这些患者中，miR-126 和 miR-451 的肿瘤表达以及生物标志物 、 、 、 、 和 的表达减少。
参与肿瘤生长、血管生成、迁移和凋亡的机制的生物标志物在患有基础呼吸疾病的患者的肿瘤中表达不同。这些发现揭示了在患有慢性呼吸系统疾病的患者中，报告的发生 LC 的风险增加的潜在生物学机制。所有 LC 患者都应确定是否存在基础呼吸疾病，因为不同的生物学特征可能有助于确定肿瘤进展和治疗反应。此外，表观遗传事件为药物治疗靶点提供了一个契机。
