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J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Glioblastoma (GBM) is the most aggressive brain tumor, with a median survival of approximately 15 months despite multimodal therapy. Although ethanol (EtOH) exposure has been associated with tumor-promoting inflammatory and signaling alterations, the molecular mediators linking EtOH to GBM progression remain poorly defined. We used Ingenuity Pathway Analysis (IPA) to construct independent EtOH- and ADAM17-associated molecular networks and identify shared regulatory effectors. Comparison of 921 EtOH-associated and 594 ADAM17-associated molecules identified 97 overlapping molecules, of which 25 were retained as high-confidence shared effectors. IPA disease-association analysis identified GBM as the strongest disease association in both the ADAM17 and integrated EtOH\u2013ADAM17 networks. Computational network perturbation analyses indicated that simulated removal of ADAM17 eliminated the GBM disease association, whereas retention of ADAM17 as the central hub produced only a partial association, supporting its role as a key regulator within the predicted network. Analysis of TCGA-GBM transcriptomic data identified significant upregulation of ADAM17, CAV1, FLNA, and CASP8. Canonical pathway analysis further identified enrichment of ADAM17-associated signaling pathways, including sheddase, EGFR, ERBB4, neuregulin, JAK\/IL-6, and matrix metalloproteinase signaling. Collectively, these findings support a candidate EtOH\u2013ADAM17 molecular axis associated with GBM progression, providing a rationale for experimental evaluation of ADAM17 as a therapeutic target.<\/jats:p>","DOI":"10.3390\/ijms27177837","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T15:08:43Z","timestamp":1788275323000},"page":"7837","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated Network and Transcriptomic Analyses Identify a Candidate Ethanol\u2013ADAM17 Molecular Axis Associated with Glioblastoma Progression"],"prefix":"10.3390","volume":"27","author":[{"given":"Aakash","family":"Arumugam","sequence":"first","affiliation":[{"name":"Institute of NeuroImmune Pharmacology, Seton Hall University, South Orange, NJ 07079, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Hannah","family":"Baik","sequence":"additional","affiliation":[{"name":"Institute of NeuroImmune Pharmacology, Seton Hall University, South Orange, NJ 07079, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nayoung","family":"Jang","sequence":"additional","affiliation":[{"name":"Institute of NeuroImmune Pharmacology, Seton Hall University, South Orange, NJ 07079, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Wenfei","family":"Huang","sequence":"additional","affiliation":[{"name":"Institute of NeuroImmune Pharmacology, Seton Hall University, South Orange, NJ 07079, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"software","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3865-4280","authenticated-orcid":false,"given":"Sulie L.","family":"Chang","sequence":"additional","affiliation":[{"name":"Institute of NeuroImmune Pharmacology, Seton Hall University, South Orange, NJ 07079, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1007\/s00401-016-1545-1","article-title":"The 2016 World Health Organization Classification of Tumors of the Central Nervous System: A summary","volume":"131","author":"Louis","year":"2016","journal-title":"Acta Neuropathol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1093\/jnen\/61.3.215","article-title":"The WHO classification of tumors of the nervous system","volume":"61","author":"Kleihues","year":"2002","journal-title":"J. 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