{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T21:13:51Z","timestamp":1783113231015,"version":"3.54.6"},"reference-count":61,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T00:00:00Z","timestamp":1674604800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["HL-125128"],"award-info":[{"award-number":["HL-125128"]}]},{"name":"National Institutes of Health","award":["AI-133351"],"award-info":[{"award-number":["AI-133351"]}]},{"name":"National Institutes of Health","award":["TSGH-E-111235"],"award-info":[{"award-number":["TSGH-E-111235"]}]},{"DOI":"10.13039\/100000060","name":"NIAID","doi-asserted-by":"publisher","award":["HL-125128"],"award-info":[{"award-number":["HL-125128"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"NIAID","doi-asserted-by":"publisher","award":["AI-133351"],"award-info":[{"award-number":["AI-133351"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"NIAID","doi-asserted-by":"publisher","award":["TSGH-E-111235"],"award-info":[{"award-number":["TSGH-E-111235"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010425","name":"Tri-Service General Hospital","doi-asserted-by":"publisher","award":["HL-125128"],"award-info":[{"award-number":["HL-125128"]}],"id":[{"id":"10.13039\/501100010425","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010425","name":"Tri-Service General Hospital","doi-asserted-by":"publisher","award":["AI-133351"],"award-info":[{"award-number":["AI-133351"]}],"id":[{"id":"10.13039\/501100010425","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010425","name":"Tri-Service General Hospital","doi-asserted-by":"publisher","award":["TSGH-E-111235"],"award-info":[{"award-number":["TSGH-E-111235"]}],"id":[{"id":"10.13039\/501100010425","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Tumor recurrence poses a significant challenge to the clinical management of stage I lung adenocarcinoma after curative surgical resection. Matrix metalloproteinases (MMPs) increase expression and correlate with recurrence and metastasis in surgically resected non-small cell lung cancer. However, the impact of MMPs on survival outcome varies, and their roles in patients with stage I lung adenocarcinoma remain unclear. In two discovery cohorts, we first analyzed 226 stage I\u2013II lung adenocarcinoma cases in the GSE31210 cohort using a clustering-based method and identified a 150-gene MMP cluster with increased expression in tumors associated with worse survival outcomes. A similar analysis was performed on 517 lung adenocarcinoma cases in the Cancer Genome Atlas cohort. A 185-gene MMP cluster was identified, which also showed increased expression in tumors and correlated with poor survival outcomes. We further streamlined from the discovery cohorts a 36-gene MMP signature significantly associated with recurrence and worse overall survival in patients with stage I lung adenocarcinoma after surgical resection. After adjusting for covariates, the high MMP-gene signature expression remained an independent risk factor. In addition, the MMP-gene signature showed enrichment in epidermal growth factor receptor wild-type lung tumors, especially for those with Kirsten rat sarcoma virus mutations. Using an independent validation cohort, we further validated the MMP-gene signature in 70 stage I lung adenocarcinoma cases. In conclusion, MMP-gene signature is a potential predictive and prognostic biomarker to stratify patients with stage I lung adenocarcinoma into subgroups based on their risk of recurrence for aiding physicians in deciding the personalized adjuvant therapeutics.<\/jats:p>","DOI":"10.3390\/ijms24032382","type":"journal-article","created":{"date-parts":[[2023,1,26]],"date-time":"2023-01-26T01:57:07Z","timestamp":1674698227000},"page":"2382","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Matrix Metallopeptidase-Gene Signature Predicts Stage I Lung Adenocarcinoma Survival Outcomes"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8998-4098","authenticated-orcid":false,"given":"Chia-Hsin","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Environmental and Occupational Health, School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA"},{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2028-2087","authenticated-orcid":false,"given":"Yuanpu Peter","family":"Di","sequence":"additional","affiliation":[{"name":"Department of Environmental and Occupational Health, School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21708","article-title":"Cancer statistics, 2022","volume":"72","author":"Siegel","year":"2022","journal-title":"CA Cancer J. 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