{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T11:42:06Z","timestamp":1776253326638,"version":"3.50.1"},"reference-count":49,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"publisher","award":["2023YFA0915700"],"award-info":[{"award-number":["2023YFA0915700"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Lung cancer recurrence and metastasis are major causes of cancer-related mortality, but the molecular determinants underlying these processes remain incompletely understood. This study aimed to identify key regulators of lung cancer progression through integrative analyses of bulk and single-cell transcriptomic datasets. Methods: Bulk transcriptomic and single-cell RNA sequencing data from multiple cohorts were integrated to identify genes associated with survival, recurrence, and metastasis. Tumor microenvironment features were further analyzed to prioritize core progression-related genes. ANLN was subsequently evaluated in independent single-cell datasets, followed by functional validation using CRISPR\u2013Cas9-mediated gene knockout in lung cancer cells. Network-based drug prediction and molecular docking were performed to identify candidate compounds targeting ANLN-related programs. Results: ANLN was identified as a core progression-related gene associated with poor prognosis. ANLN was upregulated in recurrent and metastatic lung tumors and correlated with worse overall survival. Single-cell analyses showed that ANLN was predominantly expressed in epithelial and proliferating tumor cells and was associated with microenvironment remodeling, enhanced proliferative and migratory programs, and progression toward an invasive phenotype. These findings were validated in an independent single-cell dataset capturing the transition from in situ to invasive lung cancer. Functional experiments showed that ANLN deletion reduced proliferation and promoted apoptosis in lung cancer cells. Drug prediction and molecular docking identified several candidate compounds, among which Trifluridine and Monobenzone showed favorable binding potential and pro-apoptotic effects in lung cancer cells. Conclusions: ANLN is a potential regulator of lung cancer recurrence and metastasis and marks a conserved invasion-prone epithelial state. ANLN-associated pathways may represent potential therapeutic targets in lung cancer.<\/jats:p>","DOI":"10.3390\/genes17040461","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T10:30:23Z","timestamp":1776249023000},"page":"461","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multi-Omics Analyses Identify ANLN as a Prognostic Biomarker for Recurrence and Metastasis in Non-Small Cell Lung Cancer"],"prefix":"10.3390","volume":"17","author":[{"given":"Haiwei","family":"Quan","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen 518055, China"},{"name":"Department of Biopharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Shenzhen University of Advanced Technology, Shenzhen 518107, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiguang","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Biopharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Shenzhen University of Advanced Technology, Shenzhen 518107, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lizhen","family":"Huo","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen 518055, China"},{"name":"Department of Biopharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Shenzhen University of Advanced Technology, Shenzhen 518107, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhibin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biopharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Shenzhen University of Advanced Technology, Shenzhen 518107, China"},{"name":"Center for Cancer Immunotherapy, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518172, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,15]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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