https://m2.mtmt.hu/ eng 2026-06-13 04:56 JournalArticle 33754849 APPROVED true Department of Bioinformatics, Semmelweis University, Tűzoltó utca 7-9, Budapest, 1094, Hungary Doctoral School of Pathological Sciences, Semmelweis University, Üllői út 26, Budapest, 1085, Hungary National Laboratory for Drug Research and Development, Magyar tudósok körútja 2 1117, Budapest, Hungary Research Centre for Natural Sciences, Oncology Biomarker Research Group, Institute of Enzymology, Eötvös Loránd Research Network, Magyar Tudósok körútja 2, Budapest, 1117, Hungary Department of Pediatrics, Semmelweis University, Tűzoltó utca 7-9, Budapest, 1094, Hungary Cited By :7 Export Date: 7 February 2024 CODEN: APSCG Correspondence Address: Győrffy, B.; Department of Bioinformatics, Tűzoltó utca 7-9, Hungary; email: gyorffy.balazs@med.semmelweis-univ.hu Chemicals/CAS: atezolizumab, 1380723-44-3; durvalumab, 1428935-60-7; fibroblast growth factor receptor 3, 306781-00-0; ipilimumab, 477202-00-9; MutL protein homolog 1, 155577-96-1; nivolumab, 946414-94-4; pembrolizumab, 1374853-91-4; protein bcl 2, 219306-68-0; histone lysine methyltransferase, 9076-80-6; Biomarkers, Tumor; Histone-Lysine N-Methyltransferase; Ipilimumab; SETD7 protein, human Funding details: Nemzeti Kutatási, Fejlesztési és Innovaciós Alap, NKFIA Funding details: National Research, Development and Innovation Office, 2020-1.1.6-JÖVŐ-2021-00013, KDP-14-3/PALY-2021, RRF-2.3.1-21-2022-00015, TKP-2021-NVA-15 Funding text 1: This project was supported by the Hungary National Research, Development and Innovation Office (PharmaLab, RRF-2.3.1-21-2022-00015, TKP-2021-NVA-15, and 2020-1.1.6-JÖVŐ-2021-00013). Project no. KDP-14-3/PALY-2021 has been implemented with the support provided by the Ministry of Culture and Innovation of Hungary from the National Research, Development and Innovation Fund, financed under the KDP-2020 funding scheme. The authors acknowledge the support of ELIXIR-Hungary ( https://www.bioinformatics.hu/ ) and thank Viktoria Lakatos for the careful English editing of the manuscript. Funding text 2: This project was supported by the Hungary National Research, Development and Innovation Office (PharmaLab, RRF-2.3.1-21-2022-00015, TKP-2021-NVA-15, and 2020-1.1.6-JÖVŐ-2021-00013). Project no. KDP-14-3/PALY-2021 has been implemented with the support provided by the Ministry of Culture and Innovation of Hungary from the National Research, Development and Innovation Fund, financed under the KDP-2020 funding scheme. The authors acknowledge the support of ELIXIR-Hungary (https://www.bioinformatics.hu/ ) and thank Viktoria Lakatos for the careful English editing of the manuscript. 0 false 2026-06-09T09:39:23.118+0000 2024-02-06T12:54:16.564+0000 2023-04-17T12:48:46.953+0000 true 10019974 xSzűts xFerencné /api/admin/10019974 Admin true 10019974 2026-02-09T20:32:11.894+0000 Admin 10014568 /api/admin/10014568 Vándor Andrea true 10014568 true 2024-04-04T10:41:14.495+0000 true false true 24 24 /api/publicationtype/24 PublicationType 1 true 24 JournalArticle true 10000059 Article true 24 24 /api/publicationtype/24 PublicationType 1 true 24 JournalArticle /api/subtype/10000059 Szakcikk SubType 101 true 10000059 true 1 /api/category/1 Category true 1 Kovács, Szonja Anna Predictive biomarkers of immunotherapy response with pharmacological applications in solid tumors true true /api/journal/10551 REVIEWED true false 10551 false 10551 true 1671-4083 1745-7254 Journal FOREIGN 44 9 1879 1889 1879 11 2023 Immune-checkpoint inhibitors show promising effects in the treatment of multiple tumor types. Biomarkers are biological indicators used to select patients for a systemic anticancer treatment, but there are only a few clinically useful biomarkers such as PD-L1 expression and tumor mutational burden, which can be used to predict immunotherapy response. In this study, we established a database consisting of both gene expression and clinical data to identify biomarkers of response to anti-PD-1, anti-PD-L1, and anti-CTLA-4 immunotherapies. A GEO screening was executed to identify datasets with simultaneously available clinical response and transcriptomic data regardless of cancer type. The screening was restricted to the studies involving administration of anti-PD-1 (nivolumab, pembrolizumab), anti-PD-L1 (atezolizumab, durvalumab) or anti-CTLA-4 (ipilimumab) agents. Receiver operating characteristic (ROC) analysis and Mann-Whitney test were executed across all genes to identify features related to therapy response. The database consisted of 1434 tumor tissue samples from 19 datasets with esophageal, gastric, head and neck, lung, and urothelial cancers, plus melanoma. The strongest druggable gene candidates linked to anti-PD-1 resistance were SPIN1 (AUC = 0.682, P = 9.1E-12), SRC (AUC = 0.667, P = 5.9E-10), SETD7 (AUC = 0.663, P = 1.0E-09), FGFR3 (AUC = 0.657, P = 3.7E-09), YAP1 (AUC = 0.655, P = 6.0E-09), TEAD3 (AUC = 0.649, P = 4.1E-08) and BCL2 (AUC = 0.634, P = 9.7E-08). In the anti-CTLA-4 treatment cohort, BLCAP (AUC = 0.735, P = 2.1E-06) was the most promising gene candidate. No therapeutically relevant target was found to be predictive in the anti-PD-L1 cohort. In the anti-PD-1 group, we were able to confirm the significant correlation with survival for the mismatch-repair genes MLH1 and MSH6 . A web platform for further analysis and validation of new biomarker candidates was set up and available at https://www.rocplot.com/immune . In summary, a database and a web platform were established to investigate biomarkers of immunotherapy response in a large cohort of solid tumor samples. Our results could help to identify new patient cohorts eligible for immunotherapy. 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class="authors"> <img title="Forrásközlemény" style="float: left" src="/frontend/resources/grid/publication-core-icon.png"> <img title="Idézőközlemény" style="float: left" src="/frontend/resources/grid/publication-citation-icon.png"> <div class="autype autype0"> <span class="author-name" mtid="10081093"><a href="/gui2/?type=authors&mode=browse&sel=10081093" target="_blank">Kovács Szonja Anna (<span class="authorship-author-name">Kovács Szonja Anna</span> <span class="authorAux-mtmt"> Molekuláris biológia</span>) </a> </span> <span class="author-affil"><span title="Research Centre for Natural Sciences">RCNS</span>/<span title="Institute of Molecular Life Sciences">IMLS</span>/Enzim_417; <span title="Semmelweis University">SU</span>/<span title="Faculty of Medicine">FM</span>/<span title="Instituties">I</span>/Bioinformatika Tanszék; <span title="Semmelweis University">SU</span>/School of PhD Studies</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10063867"><a href="/gui2/?type=authors&mode=browse&sel=10063867" target="_blank">Fekete János Tibor (<span class="authorship-author-name">Fekete János Tibor</span> <span class="authorAux-mtmt"> Prediktív biomarkerek</span>) </a> </span> <span class="author-affil"><span title="Research Centre for Natural Sciences">RCNS</span>/<span title="Institute of Molecular Life Sciences">IMLS</span>/Enzim_417</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10000109"><a href="/gui2/?type=authors&mode=browse&sel=10000109" target="_blank">Győrffy Balázs ✉ (<span class="authorship-author-name">Győrffy Balázs</span> <span class="authorAux-mtmt"> Onkológia</span>) </a> </span> <span class="author-affil"><span title="Research Centre for Natural Sciences">RCNS</span>/<span title="Institute of Molecular Life Sciences">IMLS</span>/Enzim_417; <span title="Semmelweis University">SU</span>/<span title="Faculty of Medicine">FM</span>/<span title="Instituties">I</span>/Bioinformatika Tanszék; <span title="Semmelweis University">SU</span>/<span title="Faculty of Medicine">FM</span>/<span title="Clinical">C</span>/Department of Pediatrics</span> </div> </div> <div class="title"><a href="/gui2/?mode=browse&params=publication;33754849" target="_blank">Predictive biomarkers of immunotherapy response with pharmacological applications in solid tumors</a></div> <div> <span class="journal-title">ACTA PHARMACOLOGICA SINICA</span> <span class="journal-issn">(<a target="_blank" href="https://portal.issn.org/resource/ISSN/1671-4083">1671-4083</a> <a target="_blank" href="https://portal.issn.org/resource/ISSN/1745-7254">1745-7254</a>)</span>: <span class="journal-volume">44</span> <span class="journal-issue">9</span> <span class="page"> pp 1879-1889 </span> <span class="year">(2023)</span> </div> <div class="pub-footer"> <span class="language" xmlns="http://www.w3.org/1999/html">Language: English | </span> <span class="identifiers"> <span class="id identifier oa_GOLD" title=" Gold "> <a style="color:blue" title="10.1038/s41401-023-01079-6" target="_blank" href="https://doi.org/10.1038/s41401-023-01079-6"> DOI </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="000970965200001" target="_blank" href="https://www.webofscience.com/wos/woscc/full-record/000970965200001"> WoS </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="85152646595" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-85152646595"> Scopus </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="37055532" target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=37055532&dopt=Abstract"> PubMed </a> </span> <span class="id identifier oa_NONE" title=" None "> <a style="color:blue" title="https://www.scopus.com/inward/record.uri?eid=2-s2.0-85152646595&doi=10.1038%2Fs41401-023-01079-6&partnerID=40&md5=976dbeadcfdb60024eec42b09b6cb2c2" target="_blank" href="https://www.scopus.com/inward/record.uri?eid=2-s2.0-85152646595&doi=10.1038%2Fs41401-023-01079-6&partnerID=40&md5=976dbeadcfdb60024eec42b09b6cb2c2"> Other URL </a> </span> </span> <OnlyViewableByAuthor><div class="ratings"> <div class="journal-subject">Journal subject: Scopus - Medicine (miscellaneous)&nbsp;&nbsp;&nbsp;Rank:&nbsp;D1</div> <div class="journal-subject">Journal subject: Scopus - Pharmacology (medical)&nbsp;&nbsp;&nbsp;Rank:&nbsp;D1</div> <div class="journal-subject">Journal subject: Scopus - Pharmacology&nbsp;&nbsp;&nbsp;Rank:&nbsp;D1</div> </div></OnlyViewableByAuthor> <div class="publication-citation" style="margin-left: 0.5cm;"> <span title="" class="citingPub-count">Citing papers: 156</span> | Independent citation: 150 | Self citation: 6 | Unknown citation: 0 | Number of citations in WoS: 150 | Number of citations in Scopus:&nbsp;101 | WoS/Scopus assigned:&nbsp;156 | Number of citations with DOI:&nbsp;156 </div> <div class="publication-citation"> <a target="_blank" href="/api/publication?cond=citations.related;eq;33754849&sort=publishedYear,desc&sort=title"> Number of cited publications: 4 </a> </div> <div class="mtid"><span class="long-pub-mtid">Publication: 33754849</span> | <span class="status-data status-APPROVED"> Published </span> Core Citing | <span class="type-subtype">Journal Article ( Article ) </span> | <span class="pub-category">Scientific</span> | <span class="publication-sourceOfData">kézi felvitel</span> </div> <div class="funder"> (Open access funding provided by Semmelweis University), Nemzeti Gyógyszerkutatási és Fejlesztési Laboratórium (PharmaLab)(RRF-2.3.1-21-2022-00015) Funder: NRDIO, National Laboratory of Translational Neuroscience (TINL)(RRF-2.3.1-21-2022-00011), (TKP-2021-NVA-15) Funder: NRDIO, (2020-1.1.6-JOVO-2021-00013), (KDP-14-3/PALY-2021), (ELIXIR Hungary) </div> <div class="lastModified">Last Modified: 2024.02.06. 13:54 Kinga Sonnevend (SE_AOK_Adm5_Élet_kutcsop, admin) </div> <div class="lockedBy">Centrally managed 2024.04.04. 12:41 Andrea Vándor (VA, admin) </div> <pre class="comment" style="margin-top: 0; margin-bottom: 0;"><u>Comments</u>: Department of Bioinformatics, Semmelweis University, Tűzoltó utca 7-9, Budapest, 1094, Hungary Doctoral School of Pathological Sciences, Semmelweis University, Üllői út 26, Budapest, 1085, Hungary National Laboratory for Drug Research and Development, Magyar tudósok körútja 2 1117, Budapest, Hungary Research Centre for Natu...</pre> </div></div>