{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T12:13:12Z","timestamp":1756901592191,"version":"3.44.0"},"reference-count":74,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Metastasis is one of the leading factors of cancer-related deaths worldwide. New potential targets and treatment strategies are needed to extend survival and enhance the quality of life for these patients. We performed an in-depth bioinformatics analysis to identify potential genes and associated potential therapeutic compounds for metastasis of prostate adenocarcinoma.<\/jats:p>\n               <jats:p>The differentially expressed genes (DEGs) were first identified using four datasets (GSE8511), (GSE3325), (GSE27616) and (GSE6919) present in the Gene Expression Omnibus (GEO) database and analyzed using the GEO2R. WGCNA was performed to find a significant gene cluster. Network analysis was performed using MCODE and Cytohubba plugins of Cytoscape to select hub genes. Moreover, expression validation of key genes was carried out using the TCGA dataset. Functional annotation and pathway enrichment analyses were conducted for validation, while survival analysis was applied to assess potential therapeutic effects. DEGs retrieved from the GEO were submitted to the Connectivity Map database to identify potentially related compounds. Molecular docking, ADMET analysis and drug-likeness properties, MD simulations and MM-GBSA analysis were performed to screen for the best potential drugs.<\/jats:p>\n               <jats:p>We identified three compounds\u2014Prunetin, Ofloxacin, and ALW-II-49-7 that may help extend disease-free survival in patients with tumor metastasis. Additionally, ACTA2, MYLK, and CNN1 were recognized as potential therapeutic targets for these compounds. These drugs\u2019 potential effectiveness and binding efficiency were screened using induced fit molecular docking followed by 100\u00a0ns MD-based Simulations and MM-GBSA analysis. However, further in vitro and in vivo studies are needed to confirm these findings.<\/jats:p>\n               <jats:p>Insight box This study integrates microarray gene expression profiling with bioinformatics tools to identify differentially expressed genes (DEGs) and co-expression networks using WGCNA. Network analysis in Cytoscape was used to screen hub genes, and the Connectivity Map (cMAP) database was searched for potential candidate drugs. Binding efficiency of repurposed drugs was evaluated using molecular docking, molecular dynamics (MD) simulations, and MM-GBSA analysis. Our findings provide the potential therapeutic drugs and targets of prostate adenocarcinoma metastasis with possibilities for follow-up in vitro and in vivo validation.<\/jats:p>","DOI":"10.1093\/intbio\/zyaf016","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T10:03:42Z","timestamp":1755857022000},"source":"Crossref","is-referenced-by-count":0,"title":["Integrative bioinformatics and drug repurposing for metastatic prostate cancer: identifying novel therapeutic targets by transcriptional profiling and molecular Modeling"],"prefix":"10.1093","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1123-430X","authenticated-orcid":false,"given":"Haseeb","family":"Nisar","sequence":"first","affiliation":[{"name":"Interdisciplinary Research Centre for Finance and Digital Economy, King Fahd University of Petroleum & Minerals , Academic Belt Road Dhahran 31261, Eastern Province ,","place":["Saudi Arabia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jignesh","family":"Prajapati","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Forensic Science, University School of Sciences, Gujarat University , University Road, Navrangpura, Ahmedabad, 380009, Gujarat ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asma Muhammad","family":"Mumtaz","sequence":"additional","affiliation":[{"name":"Department of Life-Sciences, University of Management and Technology , C-II Block C 2, Phase 1, Johar Town, Lahore, 54770, Punjab ,","place":["Pakistan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atiqa","family":"Iftikhar","sequence":"additional","affiliation":[{"name":"Department of Life-Sciences, University of Management and Technology , C-II Block C 2, Phase 1, Johar Town, Lahore, 54770, Punjab ,","place":["Pakistan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Faria","family":"Faran","sequence":"additional","affiliation":[{"name":"Department of Life-Sciences, University of Management and Technology , C-II Block C 2, Phase 1, Johar Town, Lahore, 54770, Punjab ,","place":["Pakistan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rimsha Hamid","family":"Mehmood","sequence":"additional","affiliation":[{"name":"Department of Life-Sciences, University of Management and Technology , C-II Block C 2, Phase 1, Johar Town, Lahore, 54770, Punjab ,","place":["Pakistan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samiah","family":"Shahid","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Biotechnology, The University of Lahore , 1-Km Defence Road, near Bhuptian Chowk\u060c, Lahore, 54770, Punjab ,","place":["Pakistan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dweipayan","family":"Goswami","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Biotechnology, University School of Sciences, Gujarat University , University Road, Navrangpura, Ahmedabad, 380009, Gujarat ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,8,22]]},"reference":[{"key":"2025082206033886900_ref1","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J Clin"},{"journal-title":"Organization","year":"2020","author":"I. 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