Mateu-Jimenez, MercèCurull Serrano, VíctorRodríguez-Fuster, AlbertoAguiló Espases, RafaelSánchez-Font, AlbertPijuan Andujar, LaraGea Guiral, JoaquimBarreiro Portela, Esther2018-10-262018-10-262018Mateu-Jimenez M, Curull V, Rodríguez-Fuster A, Aguiló R, Sánchez-Font A, Pijuan L. et al. Profile of epigenetic mechanisms in lung tumors of patients with underlying chronic respiratory conditions. Clin Epigenetics. 2018 Jan 16;10:7. DOI: 10.1186/s13148-017-0437-01868-7075http://hdl.handle.net/10230/35664BACKGROUND: 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. METHODS: 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, N = 20/group). RESULTS: 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 PTEN, MARCKs, TPM-1, PDCD4, SPRY-2, ETS-1, ZEB-2, FGFRL-1, EFNA-3, and k-RAS together with P53 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 PTEN, MARCKs, FGFRL-1, SNAIL-1, P63, and k-RAS were reduced. CONCLUSIONS: 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 targetsapplication/pdfengCopyright © The Author(s). 2018. Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise statedPulmons -- Càncerinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1186/s13148-017-0437-0DNA methylationIncreased susceptibility to lung cancerLung tumorigenesis biomarkersTumor microRNAsUnderlying chronic respiratory diseaseinfo:eu-repo/semantics/openAccess