{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T11:34:17Z","timestamp":1767008057837,"version":"3.41.2"},"reference-count":46,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Public Ministry of Labor Campinas"},{"DOI":"10.13039\/501100001707","name":"Union for International Cancer Control","doi-asserted-by":"publisher","award":["Technical Fellowship Award to DM"],"award-info":[{"award-number":["Technical Fellowship Award to DM"]}],"id":[{"id":"10.13039\/501100001707","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2018\/ 10511-6"],"award-info":[{"award-number":["2018\/ 10511-6"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018219","name":"Hospital de C\u00e2ncer de Barretos","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018219","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Oncology Care Support Program"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Ther Adv Med Oncol"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:sec><jats:title>Introduction:<\/jats:title><jats:p> Glioblastoma (GBM), isocitrate dehydrogenase ( IDH) wild-type ( IDH<jats:sup>wt<\/jats:sup>), and grade 4 astrocytomas, IDH mutant ( IDH<jats:sup>mut<\/jats:sup>), are the most common and aggressive primary malignant brain tumors in adults. A better understanding of the tumor immune microenvironment may provide new biomarkers and therapeutic opportunities. <\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives:<\/jats:title><jats:p> We aimed to evaluate the expression profile of 730 immuno-oncology-related genes in patients with IDH<jats:sup>wt<\/jats:sup> GBM and IDH<jats:sup>mut<\/jats:sup> tumors and identify prognostic biomarkers and a gene signature associated with patient survival. <\/jats:p><\/jats:sec><jats:sec><jats:title>Methods:<\/jats:title><jats:p> RNA was isolated from formalin-fixed, paraffin-embedded sections of 99 tumor specimens from patients treated with standard therapy. Gene expression profile was assessed using the Pan-Cancer Immune Profiling Panel (Nanostring Technologies, Inc., Seattle, WA, USA). Data analysis was performed using nSolverSoftware and validated in The Cancer Genome Atlas. In addition, we developed a prognostic signature using the cox regression algorithm (Least Absolute Shrinkage and Selection Operator). <\/jats:p><\/jats:sec><jats:sec><jats:title>Results:<\/jats:title><jats:p> We found 88 upregulated genes, high immunological functions, and a high macrophage score in IDH<jats:sup>wt<\/jats:sup> GBM compared to IDH<jats:sup>mut<\/jats:sup> tumors. Regarding IDH<jats:sup>wt<\/jats:sup> GBM, we found 24 upregulated genes in short-term survivors (STS) and overexpression of CD274 (programmed death-ligand 1, PD-L1). Immune pathways, CD45, cytotoxic, and macrophage scores were upregulated in STS. Two different prognostic groups were found based on the 12-gene signature (CXCL14, PSEN2, TNFRSF13C, IL13RA1, MAP2K1, TNFSF14, THY1, CTSL, ITGAE, CHUK, CD207, and IFITM1). <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion:<\/jats:title><jats:p> The elevated expression of immune-oncology-related genes was associated with worse outcome in IDH<jats:sup>wt<\/jats:sup> GBM patients. Increased immune functions, CD45, cytotoxic cells, and macrophage scores were associated with a more aggressive phenotype and may provide promising possibilities for therapy. Moreover, a 12 gene-based signature could predict patients\u2019 prognosis. <\/jats:p><\/jats:sec>","DOI":"10.1177\/17588359221127678","type":"journal-article","created":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T11:35:11Z","timestamp":1671622511000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["Cancer immune profiling unveils biomarkers, immunological pathways, and cell type score associated with glioblastoma patients\u2019 survival"],"prefix":"10.1177","volume":"14","author":[{"given":"Daniel Antunes","family":"Moreno","sequence":"first","affiliation":[{"name":"Molecular Oncology Research Center, Barretos, S\u00e3o Paulo, Brazil"}]},{"given":"Luciane Sussuchi","family":"da Silva","sequence":"additional","affiliation":[{"name":"Molecular Oncology Research Center, Barretos, S\u00e3o Paulo, Brazil"}]},{"given":"Isabella","family":"Gomes","sequence":"additional","affiliation":[{"name":"Molecular Oncology Research Center, Barretos, S\u00e3o Paulo, Brazil"}]},{"given":"Let\u00edcia Ferro","family":"Leal","sequence":"additional","affiliation":[{"name":"Molecular Oncology Research Center, Barretos, S\u00e3o Paulo, Brazil"}]},{"given":"Gustavo Noriz","family":"Berardinelli","sequence":"additional","affiliation":[{"name":"Department of Molecular Diagnosis, Barretos, S\u00e3o Paulo, Brazil"}]},{"given":"Gisele Melo","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Barretos, S\u00e3o Paulo, Brazil"}]},{"given":"Caio Augusto","family":"Pereira","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Barretos, S\u00e3o Paulo, Brazil"}]},{"given":"Iara Viana Vidigal","family":"Santana","sequence":"additional","affiliation":[{"name":"Pathology Department, BCH, Barretos, S\u00e3o Paulo, Brazil"}]},{"given":"Marcus de Medeiros","family":"Matsushita","sequence":"additional","affiliation":[{"name":"Pathology Department, BCH, Barretos, S\u00e3o Paulo, Brazil"}]},{"given":"Krishna","family":"Bhat","sequence":"additional","affiliation":[{"name":"Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"}]},{"given":"Sean","family":"Lawler","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, MA, USA Brown University, Pathology and Laboratory Medicine, Providence, Rhode Island, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9639-7940","authenticated-orcid":false,"given":"Rui Manuel","family":"Reis","sequence":"additional","affiliation":[{"name":"Molecular Oncology Research Center, Barretos Cancer Hospital, Rua Antenor Duarte Villela, 1331, Barretos, S\u00e3o Paulo CEP 14784 400, Brazil"},{"name":"Department of Molecular Diagnosis, Barretos, S\u00e3o Paulo, Brazil ICVS\/3B\u2019s PT Government Associate Laboratory, Braga\/Guimar\u00e3es, Portugal Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal"}]}],"member":"179","published-online":{"date-parts":[[2022,12,21]]},"reference":[{"key":"bibr1-17588359221127678","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noz150"},{"key":"bibr2-17588359221127678","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noab106"},{"key":"bibr3-17588359221127678","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-016-1545-1"},{"key":"bibr4-17588359221127678","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2009.12.020"},{"key":"bibr5-17588359221127678","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2015.242"},{"key":"bibr6-17588359221127678","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa043330"},{"key":"bibr7-17588359221127678","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2017.18718"},{"key":"bibr8-17588359221127678","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci8010015"},{"key":"bibr9-17588359221127678","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-020-03675-6"},{"key":"bibr10-17588359221127678","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-019-0224-7"},{"key":"bibr11-17588359221127678","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-16-2310"},{"key":"bibr12-17588359221127678","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.25611"},{"key":"bibr13-17588359221127678","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2013.256"},{"key":"bibr14-17588359221127678","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-015-0088-7"},{"key":"bibr15-17588359221127678","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v039.i05"},{"key":"bibr16-17588359221127678","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0020588."},{"key":"bibr17-17588359221127678","first-page":"33","volume":"13","author":"Bozdag S","year":"2014","journal-title":"Cancer Inform"},{"key":"bibr18-17588359221127678","doi-asserted-by":"publisher","DOI":"10.1007\/s11910-013-0345-4"},{"key":"bibr19-17588359221127678","doi-asserted-by":"publisher","DOI":"10.20892\/j.issn.2095-3941.2019.0353"},{"key":"bibr20-17588359221127678","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2009.02.011"},{"key":"bibr21-17588359221127678","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.26863"},{"key":"bibr22-17588359221127678","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1402164"},{"key":"bibr23-17588359221127678","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2011.112"},{"key":"bibr24-17588359221127678","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.6560."},{"key":"bibr25-17588359221127678","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.04.084"},{"key":"bibr26-17588359221127678","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-020-02140-x"},{"key":"bibr27-17588359221127678","doi-asserted-by":"publisher","DOI":"10.1038\/s41417-019-0140-8"},{"key":"bibr28-17588359221127678","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2018.01.012"},{"key":"bibr29-17588359221127678","doi-asserted-by":"publisher","DOI":"10.2174\/1381612822666151210122954"},{"key":"bibr30-17588359221127678","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04355-w"},{"key":"bibr31-17588359221127678","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1202802"},{"key":"bibr32-17588359221127678","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2017.04.005"},{"key":"bibr33-17588359221127678","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.11828"},{"key":"bibr34-17588359221127678","doi-asserted-by":"publisher","DOI":"10.2174\/156720111793663570"},{"key":"bibr35-17588359221127678","doi-asserted-by":"publisher","DOI":"10.1002\/path.4072"},{"key":"bibr36-17588359221127678","doi-asserted-by":"publisher","DOI":"10.18632\/aging.103065"},{"key":"bibr37-17588359221127678","doi-asserted-by":"publisher","DOI":"10.1186\/1476-4598-5-39"},{"key":"bibr38-17588359221127678","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/now034"},{"key":"bibr39-17588359221127678","doi-asserted-by":"publisher","DOI":"10.1038\/s41374-019-0345-3"},{"key":"bibr40-17588359221127678","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-018-0591-4"},{"key":"bibr41-17588359221127678","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12952"},{"key":"bibr42-17588359221127678","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/925135."},{"key":"bibr43-17588359221127678","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-12-2271"},{"key":"bibr44-17588359221127678","first-page":"333","volume":"22","author":"Iwata R","year":"2020","journal-title":"Neuro Oncol"},{"key":"bibr45-17588359221127678","doi-asserted-by":"publisher","DOI":"10.1038\/srep19085"},{"key":"bibr46-17588359221127678","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.01015"}],"container-title":["Therapeutic Advances in Medical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/17588359221127678","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/17588359221127678","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/17588359221127678","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T22:06:24Z","timestamp":1740780384000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/17588359221127678"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1]]},"references-count":46,"alternative-id":["10.1177\/17588359221127678"],"URL":"https:\/\/doi.org\/10.1177\/17588359221127678","relation":{},"ISSN":["1758-8359","1758-8359"],"issn-type":[{"type":"print","value":"1758-8359"},{"type":"electronic","value":"1758-8359"}],"subject":[],"published":{"date-parts":[[2022,1]]},"article-number":"17588359221127678"}}