{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,23]],"date-time":"2025-11-23T05:13:41Z","timestamp":1763874821698,"version":"3.45.0"},"reference-count":59,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T00:00:00Z","timestamp":1763683200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["2022.11242.BD"],"award-info":[{"award-number":["2022.11242.BD"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Rog\u00e9rio Ribeiro","doi-asserted-by":"publisher","award":["BD\/07092\/2021"],"award-info":[{"award-number":["BD\/07092\/2021"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"crossref","award":["NORTE-01\u20130145-FEDER\u2013072678"],"award-info":[{"award-number":["NORTE-01\u20130145-FEDER\u2013072678"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Aberrant or loss of cell adhesion drives invasion and metastasis, key hallmarks of cancer progression. In this work, we hypothesized that a gene signature related to cell adhesion could predict breast cancer prognosis. Methods: Highly variant genes were tested for association with overall survival using Cox regression. Adhesion-related genes were identified through gene ontology analysis and multivariate Cox regression, with AIC selection, defined the prognostic signature. The AdhesionScore was then calculated as a weighted sum of gene expression, with risk stratification assessed by Kaplan\u2013Meier and log-rank tests. Results: We found that the AdhesionScore was a significant independent predictor of poor survival in three large independent datasets, as it provided a robust stratification of patient prognosis in the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) (HR: 2.65; 95% CI: 2.33\u20133.0, p = 2.34 \u00d7 10\u221251), The Cancer Genome Atlas (TCGA) (HR: 3.46; 95% CI: 2.35\u20135.09, p = 3.50 \u00d7 10\u221210), and the GSE96058 (HR: 2.83; 95% CI: 2.20\u20133.65, p = 6.29 \u00d7 10\u221216) datasets. The 5-year risk of death in the high-risk group was 32.41% for METABRIC, 27.8% for TCGA, and 17.54% for GSE96058 datasets. Consistently, HER2-enriched and triple-negative breast carcinomas (TNBC) cases showed higher AdhesionScores than luminal subtypes, indicating an association with aggressive tumor biology. Conclusions: We have developed, for the first time, a molecular signature based on cell adhesion, as well as an associated AdhesionScore that can predict patient prognosis in invasive breast cancer, with potential clinical application. We developed a novel adhesion-based molecular signature, the AdhesionScore, that robustly predicts prognosis in breast cancer across independent cohorts, highlighting its potential clinical utility for patient risk stratification.<\/jats:p>","DOI":"10.3390\/cancers17233731","type":"journal-article","created":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T14:17:23Z","timestamp":1763734643000},"page":"3731","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["AdhesionScore: A Prognostic Predictor of Breast Cancer Patients Based on a Cell Adhesion-Associated Gene Signature"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3832-2027","authenticated-orcid":false,"given":"Catarina","family":"Esqu\u00edvel","sequence":"first","affiliation":[{"name":"Cancer Metastasis, i3S, Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"ICBAS, Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, 4050-313 Porto, Portugal"}]},{"given":"Rog\u00e9rio","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Department of Computer Science, Faculty of Sciences, University of Porto, Rua do Campo Alegre 1055, 4169-007 Porto, Portugal"},{"name":"Laboratory of Artificial Intelligence and Decision Support, Institute for Systems and Computer Engineering, Technology and Science, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9698-9233","authenticated-orcid":false,"given":"Ana Sofia","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Cancer Metastasis, i3S, Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"IPATIMUP, Instituto de Patologia e Imunologia Molecular da Universidade do Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3838-8664","authenticated-orcid":false,"given":"Pedro G.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Department of Computer Science, Faculty of Sciences, University of Porto, Rua do Campo Alegre 1055, 4169-007 Porto, Portugal"},{"name":"Laboratory of Artificial Intelligence and Decision Support, Institute for Systems and Computer Engineering, Technology and Science, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1076-1343","authenticated-orcid":false,"given":"Joana","family":"Paredes","sequence":"additional","affiliation":[{"name":"Cancer Metastasis, i3S, Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"IPATIMUP, Instituto de Patologia e Imunologia Molecular da Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"FMUP, Faculdade de Medicina da Universidade do Porto, 4200-319 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: The next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.bbcan.2012.05.002","article-title":"Epithelial E- and P-cadherins: Role and clinical significance in cancer","volume":"1826","author":"Paredes","year":"2012","journal-title":"Biochim. 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