{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T03:14:05Z","timestamp":1788146045644,"version":"build-2803163510"},"reference-count":64,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T00:00:00Z","timestamp":1787961600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Shanghai Sixth People\u2019s Hospital","award":["ynts202411"],"award-info":[{"award-number":["ynts202411"]}]},{"award":["ynts202411"],"award-info":[{"award-number":["ynts202411"]}],"id":[{"id":"https:\/\/ror.org\/049zrh188","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Chronic obstructive pulmonary disease (COPD) is associated with systemic inflammation and increased cardiovascular comorbidity, yet peripheral blood molecular markers for cardiovascular comorbidity-related stratification in COPD remain poorly defined. Methods: In this study, PBMC transcriptomic datasets from a COPD cohort (GSE42057) and a CAD cohort (GSE113079) were analyzed using weighted gene co-expression network analysis (WGCNA) to identify disease-associated modules, followed by overlapping gene screening. Machine-learning models were then applied to prioritize the shared genes. External validation was performed in an independent COPD cohort (GSE54837) and an independent CAD cohort (GSE250283). Immune-cell deconvolution and single-cell transcriptomic analysis of a CAD dataset (GSE269269) were further used to characterize the immune and cellular context of the leading candidate. Finally, RT\u2013qPCR was performed in an institutional PBMC cohort for experimental validation. Results: A total of 169 shared genes were identified, with enrichment in immune, mitochondrial, oxidative phosphorylation, and metabolic pathways. RTN4 was the most consistently validated candidate across COPD and CAD cohorts and was associated with poorer lung function, advanced GOLD stages, and monocyte-related immune patterns. In CAD single-cell data, RTN4-associated signals were mainly localized to monocytes, particularly intermediate monocytes under plaque rupture conditions, with enrichment of immune, antigen-presentation, oxidative-stress, and metabolic pathways. RT\u2013qPCR confirmed increased RTN4 mRNA expression in COPD and a further increase in patients with COPD and comorbid CAD despite comparable FEV1% predicted between the two COPD groups. Conclusions: These findings suggest that elevated RTN4 expression may serve as a PBMC-derived, monocyte-associated candidate molecular feature related to COPD\u2013CAD comorbidity.<\/jats:p>","DOI":"10.3390\/genes17091046","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T02:08:58Z","timestamp":1788142138000},"page":"1046","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative Transcriptomic Analysis and Single-Cell Characterization Identify RTN4 as a Candidate PBMC-Derived Hub Gene Associated with COPD and Coronary Artery Disease"],"prefix":"10.3390","volume":"17","author":[{"given":"Yongle","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Shanghai Sixth People\u2019s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Shan","family":"Shan","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Shanghai Sixth People\u2019s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]},{"given":"Hanhan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Shanghai Sixth People\u2019s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Tao","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Shanghai Sixth People\u2019s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2400516","DOI":"10.1183\/13993003.00516-2024","article-title":"20-year trends in excess costs of COPD","volume":"65","author":"Amegadzie","year":"2025","journal-title":"Eur. 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