{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T10:41:30Z","timestamp":1789296090087,"version":"build-2803163510"},"reference-count":38,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T00:00:00Z","timestamp":1759449600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science, Technological Development and Innovation of the Republic of Serbia","award":["451-03-136\/2025-03\/200007"],"award-info":[{"award-number":["451-03-136\/2025-03\/200007"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Galectin-3 (Gal-3), encoded by LGALS3, is a \u03b2-galactoside-binding lectin involved in diverse tumor-associated processes, including immune modulation, cell cycle regulation, and stress adaptation. Despite its known roles in cancer biology, the full extent of its molecular functions and prognostic relevance across tumor types remains incompletely understood. This study aimed to systematically investigate the transcriptomic impact of LGALS3 deletion and assess its clinical significance in cancer. Methods: We analyzed CRISPR-Cas9 knockout transcriptomic data from the SigCom LINCS database to characterize the consensus gene signature associated with LGALS3 loss using functional enrichment analyses. Pan-cancer survival analyses were conducted using TIMER2.0. Differential Gal-3 protein levels in ductal adenocarcinoma and normal pancreatic tissues were evaluated using the Human Protein Atlas. Finally, functional analyses were performed in pancreatic ductal adenocarcinoma (PDAC). Results: LGALS3 deletion across multiple cancer cell lines led to transcriptomic changes involving mitotic progression, stress responses, and axonal guidance pathways. High LGALS3 expression was significantly associated with worse overall survival in lower-grade glioma, PDAC, uveal melanoma, and kidney renal papillary cell carcinoma. LGALS3 knockout in YAPC cells recapitulated the pan-cancer findings, linking LGALS3 to cell morphogenesis and proliferation. Conclusions: These findings identify Galectin-3 as a key regulator of oncogenic programs and a potential prognostic biomarker in PDAC and other malignancies, with implications for therapeutic targeting.<\/jats:p>","DOI":"10.3390\/genes16101170","type":"journal-article","created":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T14:18:28Z","timestamp":1759501108000},"page":"1170","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Transcriptomic and Clinical Profiling Reveals LGALS3 as a Prognostic Oncogene in Pancreatic Cancer"],"prefix":"10.3390","volume":"16","author":[{"given":"Grazia","family":"Scuderi","sequence":"first","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9509-9098","authenticated-orcid":false,"given":"Sanja","family":"Mijatovic","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute for Biological Research \u201cSinisa Stankovic\u201d, Belgrade University, 11060 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8006-5079","authenticated-orcid":false,"given":"Danijela","family":"Maksimovic-Ivanic","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute for Biological Research \u201cSinisa Stankovic\u201d, Belgrade University, 11060 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1837-9325","authenticated-orcid":false,"given":"Michelino","family":"Di Rosa","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2272-9260","authenticated-orcid":false,"given":"Jos\u00e9 Francisco","family":"Mu\u00f1oz-Valle","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genomics, University Center of Health Sciences, University of Guadalajara, Guadalajara 44340, Jalisco, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2443-0210","authenticated-orcid":false,"given":"Alexis Missael","family":"Vizca\u00edno-Quirarte","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genomics, University Center of Health Sciences, University of Guadalajara, Guadalajara 44340, Jalisco, Mexico"},{"name":"Department of Basic Psychology, University Center of Health Sciences, University of Guadalajara, Guadalajara 44340, Jalisco, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8593-6179","authenticated-orcid":false,"given":"Gian Marco","family":"Leone","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5920-4620","authenticated-orcid":false,"given":"Katia","family":"Mangano","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6694-1992","authenticated-orcid":false,"given":"Paolo","family":"Fagone","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4570-8462","authenticated-orcid":false,"given":"Ferdinando","family":"Nicoletti","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1038\/nrc1527","article-title":"Galectins as Modulators of Tumour Progression","volume":"5","author":"Liu","year":"2005","journal-title":"Nat. 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