{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T09:08:39Z","timestamp":1779181719073,"version":"3.51.4"},"reference-count":52,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T00:00:00Z","timestamp":1777680000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science and Technology Major Project of China","award":["2024ZD0522400"],"award-info":[{"award-number":["2024ZD0522400"]}]},{"name":"China Medical and Health Development Foundation","award":["BJ2024JCHX002"],"award-info":[{"award-number":["BJ2024JCHX002"]}]},{"name":"Zhong Nanshan Medical Foundation","award":["ZNSXS-20250069"],"award-info":[{"award-number":["ZNSXS-20250069"]}]},{"name":"Yunnan Xingdian Talent Support Program \u201cFamous Medical Training Object\u201d","award":["RLMY20220004"],"award-info":[{"award-number":["RLMY20220004"]}]},{"name":"Yunnan Xingdian Talent Support Program \u201cFamous Medical Training Object\u201d","award":["RLMY20220011"],"award-info":[{"award-number":["RLMY20220011"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Chronic obstructive pulmonary disease (COPD) lacks reliable molecular biomarkers for early diagnosis and risk stratification beyond conventional spirometry-based assessment. Synthetic lethality (SL)-related gene prioritization provides a biologically informed framework for identifying disease-associated candidate biomarkers in COPD. In this study, we integrated public transcriptomic datasets, SL-related gene sets, and machine learning approaches to identify a diagnostic signature for COPD. Using GSE47460 as the training cohort (220 COPD and 108 controls) and GSE57148 as the external validation cohort (98 COPD and 91 controls), we identified 74 SL-related differentially expressed genes enriched in inflammatory signaling and extracellular matrix organization. LASSO regression and random forest analysis yielded a five-gene diagnostic signature consisting of CYP1B1, VEGFA, RET, FGG, and S100A9. The integrated nomogram showed good diagnostic performance in the validation cohort, with an AUC of 0.8311 (95% CI: 0.7839\u20130.8783), outperforming individual genes and supporting its potential use as an adjunctive molecular tool for COPD diagnosis and risk assessment. Single-cell RNA sequencing, immune infiltration analysis, and preliminary in vitro experiments further supported the biological relevance of the identified genes. Overall, this study supports SL-related gene prioritization combined with multi-omic integration as a useful strategy for COPD biomarker discovery while generating testable hypotheses regarding disease-associated vulnerability pathways.<\/jats:p>","DOI":"10.3390\/cimb48050475","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T02:06:21Z","timestamp":1777860381000},"page":"475","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Synthetic Lethality-Informed Multi-Omic Framework for Identifying a Five-Gene Diagnostic Signature in Chronic Obstructive Pulmonary Disease"],"prefix":"10.3390","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5213-490X","authenticated-orcid":false,"given":"Yue","family":"Yang","sequence":"first","affiliation":[{"name":"The First School of Clinical Medicine, Kunming Medical University, Kunming 650500, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zengrui","family":"Wang","sequence":"additional","affiliation":[{"name":"The First School of Clinical Medicine, Kunming Medical University, Kunming 650500, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaorong","family":"Su","sequence":"additional","affiliation":[{"name":"The First School of Clinical Medicine, Kunming Medical University, Kunming 650500, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiefu","family":"Tang","sequence":"additional","affiliation":[{"name":"The First School of Clinical Medicine, Kunming Medical University, Kunming 650500, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi","family":"Zhang","sequence":"additional","affiliation":[{"name":"The First School of Clinical Medicine, Kunming Medical University, Kunming 650500, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinli","family":"Fan","sequence":"additional","affiliation":[{"name":"The First School of Clinical Medicine, Kunming Medical University, Kunming 650500, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4607-4219","authenticated-orcid":false,"given":"Haitao","family":"Xu","sequence":"additional","affiliation":[{"name":"The First School of Clinical Medicine, Kunming Medical University, Kunming 650500, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lihan","family":"Wang","sequence":"additional","affiliation":[{"name":"The First School of Clinical Medicine, Kunming Medical University, Kunming 650500, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhuang","family":"Luo","sequence":"additional","affiliation":[{"name":"The First School of Clinical Medicine, Kunming Medical University, Kunming 650500, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2502244","DOI":"10.1183\/13993003.02244-2025","article-title":"Addressing the global challenges of COPD and asthma: A shared vision from the Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) and the Global Initiative for Asthma (GINA)","volume":"67","author":"Halpin","year":"2026","journal-title":"Eur. 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