{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T18:46:00Z","timestamp":1788201960435,"version":"build-2803163510"},"reference-count":35,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T00:00:00Z","timestamp":1639958400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["KAKEN 15K19061"],"award-info":[{"award-number":["KAKEN 15K19061"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["KAKEN 18K15100"],"award-info":[{"award-number":["KAKEN 18K15100"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010655","name":"Tokai University","doi-asserted-by":"publisher","award":["TOKAI UNIVERSITY SCHOOL OF MEDICINE, RESEARCH INCENTIVE ASSISTANT PLAN 2021-B04"],"award-info":[{"award-number":["TOKAI UNIVERSITY SCHOOL OF MEDICINE, RESEARCH INCENTIVE ASSISTANT PLAN 2021-B04"]}],"id":[{"id":"10.13039\/501100010655","id-type":"DOI","asserted-by":"publisher"}]},{"name":"AL-JALILA FOUNDATION","award":["AJF2018090"],"award-info":[{"award-number":["AJF2018090"]}]},{"DOI":"10.13039\/100016714","name":"University of Sharjah","doi-asserted-by":"publisher","award":["1901090258"],"award-info":[{"award-number":["1901090258"]}],"id":[{"id":"10.13039\/100016714","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Diffuse large B-cell lymphoma (DLBCL) is one of the most frequent subtypes of non-Hodgkin lymphomas. We used artificial neural networks (multilayer perceptron and radial basis function), machine learning, and conventional bioinformatics to predict the overall survival and molecular subtypes of DLBCL. The series included 106 cases and 730 genes of a pancancer immune-oncology panel (nCounter) as predictors. The multilayer perceptron predicted the outcome with high accuracy, with an area under the curve (AUC) of 0.98, and ranked all the genes according to their importance. In a multivariate analysis, ARG1, TNFSF12, REL, and NRP1 correlated with favorable survival (hazard risks: 0.3\u20130.5), and IFNA8, CASP1, and CTSG, with poor survival (hazard risks = 1.0\u20132.1). Gene set enrichment analysis (GSEA) showed enrichment toward poor prognosis. These high-risk genes were also associated with the gene expression of M2-like tumor-associated macrophages (CD163), and MYD88 expression. The prognostic relevance of this set of 7 genes was also confirmed within the IPI and MYC translocation strata, the EBER-negative cases, the DLBCL not-otherwise specified (NOS) (High-grade B-cell lymphoma with MYC and BCL2 and\/or BCL6 rearrangements excluded), and an independent series of 414 cases of DLBCL in Europe and North America (GSE10846). The perceptron analysis also predicted molecular subtypes (based on the Lymph2Cx assay) with high accuracy (AUC = 1). STAT6, TREM2, and REL were associated with the germinal center B-cell (GCB) subtype, and CD37, GNLY, CD46, and IL17B were associated with the activated B-cell (ABC)\/unspecified subtype. The GSEA had a sinusoidal-like plot with association to both molecular subtypes, and immunohistochemistry analysis confirmed the correlation of MAPK3 with the GCB subtype in another series of 96 cases (notably, MAPK3 also correlated with LMO2, but not with M2-like tumor-associated macrophage markers CD163, CSF1R, TNFAIP8, CASP8, PD-L1, PTX3, and IL-10). Finally, survival and molecular subtypes were successfully modeled using other machine learning techniques including logistic regression, discriminant analysis, SVM, CHAID, C5, C&amp;R trees, KNN algorithm, and Bayesian network. In conclusion, prognoses and molecular subtypes were predicted with high accuracy using neural networks, and relevant genes were highlighted.<\/jats:p>","DOI":"10.3390\/cancers13246384","type":"journal-article","created":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T08:43:32Z","timestamp":1639989812000},"page":"6384","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Artificial Neural Networks Predicted the Overall Survival and Molecular Subtypes of Diffuse Large B-Cell Lymphoma Using a Pancancer Immune-Oncology Panel"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6129-8299","authenticated-orcid":false,"given":"Joaquim","family":"Carreras","sequence":"first","affiliation":[{"name":"Department of Pathology, School of Medicine, Tokai University, 143 Shimokasuya, Isehara 259-1193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichiro","family":"Hiraiwa","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, Tokai University, 143 Shimokasuya, Isehara 259-1193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yara Yukie","family":"Kikuti","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, Tokai University, 143 Shimokasuya, Isehara 259-1193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Miyaoka","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, Tokai University, 143 Shimokasuya, Isehara 259-1193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sakura","family":"Tomita","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, Tokai University, 143 Shimokasuya, Isehara 259-1193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruka","family":"Ikoma","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, Tokai University, 143 Shimokasuya, Isehara 259-1193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, Tokai University, 143 Shimokasuya, Isehara 259-1193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Kondo","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, Tokai University, 143 Shimokasuya, Isehara 259-1193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Roncador","sequence":"additional","affiliation":[{"name":"Monoclonal Antibodies Unit, Spanish National Cancer Research Center (Centro Nacional de Investigaciones Oncologicas, CNIO), Melchor Fernandez Almagro 3, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6974-0806","authenticated-orcid":false,"given":"Juan F.","family":"Garcia","sequence":"additional","affiliation":[{"name":"Department of Pathology, MD Anderson Cancer Center Madrid, Calle de Arturo Soria 270, 28033 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyoshi","family":"Ando","sequence":"additional","affiliation":[{"name":"Department of Hematology, School of Medicine, Tokai University, 143 Shimokasuya, Isehara 259-1193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1402-0868","authenticated-orcid":false,"given":"Rifat","family":"Hamoudi","sequence":"additional","affiliation":[{"name":"Sharjah Institute for Medical Research, Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates"},{"name":"Division of Surgery and Interventional Science, University College London, Gower Street, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoya","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, Tokai University, 143 Shimokasuya, Isehara 259-1193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,20]]},"reference":[{"key":"ref_1","unstructured":"Brown, J.R., Freedman, A.S., and Aster, J.C. (2021). Pathobiology of Diffuse Large B Cell Lymphoma and Primary Mediastinal Large B Cell Lymphoma, UpToDate."},{"key":"ref_2","unstructured":"Aster, J.C., and Freedman, A.S. (2021). 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