{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T06:05:40Z","timestamp":1771308340046,"version":"3.50.1"},"reference-count":49,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T00:00:00Z","timestamp":1771027200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"NIH","doi-asserted-by":"publisher","award":["HL119538"],"award-info":[{"award-number":["HL119538"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"NIH","doi-asserted-by":"publisher","award":["UL1TR001425"],"award-info":[{"award-number":["UL1TR001425"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000938","name":"Veterans Administration","doi-asserted-by":"publisher","award":["I01BX002347"],"award-info":[{"award-number":["I01BX002347"]}],"id":[{"id":"10.13039\/501100000938","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000938","name":"Veterans Administration","doi-asserted-by":"publisher","award":["I01CX001891"],"award-info":[{"award-number":["I01CX001891"]}],"id":[{"id":"10.13039\/501100000938","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fondo de Investigaci\u00f3n Sanitaria","award":["PI08\/1612"],"award-info":[{"award-number":["PI08\/1612"]}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Ministerio de Sanidad y Consumo"},{"name":"SEPAR"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Lung cancer and chronic obstructive pulmonary disease (COPD) are morbid and mortal conditions arising from noxious endothelial stress. Soluble Major Histocompatibility Complex I Chain Related A (sMICA) is an activating ligand for the NKG2C receptor, and the soluble form indicates endothelial stress and is a mechanism for evading immune surveillance in lung cancer. We provide independent associations between sMICA*008 levels and the prevalence of lung cancer, lung cancer histologies, COPD, and risk factors for both diseases. Methods: We describe statistical associations between sMICA and demographic and clinical variables. Multivariate linear regression determined the independent associations between sMICA levels and lung cancer histology, between those with and without primary lung cancer, and prevalent COPD in participants without lung cancer. Point estimates and 95% confidence intervals are reported; p &lt; 0.05 is considered statistically significant. Results: The cohort (n = 586 patients) included 24% female and 48% current or former smokers. Mean sMICA were 5.20 pg\/mL \u00d7102, and FEV1%-predicted of 62. sMICA levels were higher in those who smoked vs. those who did not. In Multivariate regression, non-small cell lung cancer (NSCLC) was associated with 14.2 pg\/mL \u00d7102 (95% CI 3.57 to 24.9 pg\/mL \u00d7102) higher sMICA levels compared to those without cancer. No other histology was independently associated with higher sMICA. Primary lung cancer [12.5 pg\/mL \u00d7102 (2.85 to 22.2 pg\/mL \u00d7102)] and COPD in those without cancer [4.38 pg\/mL \u00d7102 (0.38 to 8.39 pg\/mL \u00d7102)] were associated with higher sMICA. Conclusions: sMICA*008 is independently associated with NSCLC, primary lung cancer, and COPD, respectively, in a cohort of current, former, and never smokers with and without lung cancer. sMICA levels were also higher in smokers. This study provides a foundation for future studies on sMICA activity in lung cancer and COPD, and assessment of sMICA as a biomarker for lung cancer cell type and risk of lung function loss in COPD.<\/jats:p>","DOI":"10.3390\/jcm15041496","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T08:38:39Z","timestamp":1771231119000},"page":"1496","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Soluble Major Histocompatibility Complex I-Related Chain A (sMICA)*008 Levels Associate with Smoking, Presence of Chronic Obstructive Pulmonary Disease, and Prevalence of Lung Cancer"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9718-9115","authenticated-orcid":false,"given":"Robert M.","family":"Burkes","sequence":"first","affiliation":[{"name":"Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA"},{"name":"Department of Veterans Affairs, VA\u2014Cincinnati Medical Center, Cincinnati, OH 45220, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mauricio","family":"Orozco-Levi","sequence":"additional","affiliation":[{"name":"Research Center, Fundaci\u00f3n Cardiovascular de Colombia, Calle 158 A # 23-58, Floridablanca 681004, Santander, Colombia"},{"name":"Group of Research in Muscle, Training and Lung Diseases (EMICON), Ministry of Science and Technology (MINCIENCIAS), Calle 26 # 57-83, Bogot\u00e1 111321, Colombia"},{"name":"Respiratory Department, Hospital Internacional de Colombia, Fundaci\u00f3n Cardiovascular de Colombia, Kil\u00f3metro 7 Autopista Piedecuesta, Floridablanca 681004, Santander, Colombia"},{"name":"Department of Medicine, Universidad de Santander (UDES), Calle 70 # 55-210, Bucaramanga 680006, Santander, Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alba","family":"Ramirez-Sarmiento","sequence":"additional","affiliation":[{"name":"Research Center, Fundaci\u00f3n Cardiovascular de Colombia, Calle 158 A # 23-58, Floridablanca 681004, Santander, Colombia"},{"name":"Group of Research in Muscle, Training and Lung Diseases (EMICON), Ministry of Science and Technology (MINCIENCIAS), Calle 26 # 57-83, Bogot\u00e1 111321, Colombia"},{"name":"Respiratory Department, Hospital Internacional de Colombia, Fundaci\u00f3n Cardiovascular de Colombia, Kil\u00f3metro 7 Autopista Piedecuesta, Floridablanca 681004, Santander, Colombia"},{"name":"Department of Medicine, Universidad de Santander (UDES), Calle 70 # 55-210, Bucaramanga 680006, Santander, Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1026-7908","authenticated-orcid":false,"given":"Albert","family":"Sanchez-Font","sequence":"additional","affiliation":[{"name":"Respiratory Medicine Department, Hospital del Mar, Passeig Maritim 25, 08003 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joaquin","family":"Gea","sequence":"additional","affiliation":[{"name":"Respiratory Medicine Department, Hospital del Mar, Passeig Maritim 25, 08003 Barcelona, Spain"},{"name":"Department of Medicine and Life Sciences, Universitat Pompeu Fabra (UPF), 08002 Barcelona, Spain"},{"name":"Instituto Municipal de Investigaci\u00f3n M\u00e9dica (IMIM), 08003 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael T.","family":"Borchers","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA"},{"name":"Department of Veterans Affairs, VA\u2014Cincinnati Medical Center, Cincinnati, OH 45220, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"577","DOI":"10.2217\/17520363.2.6.577","article-title":"Biomarkers in lung cancer: From early detection to novel therapeutics and decision making","volume":"2","author":"Scott","year":"2008","journal-title":"Biomark. 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