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A novel 20-gene prognostic score in pancreatic adenocarcinoma
Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers. Known risk factors for this disease are currently insufficient in predicting mortality. In order to better prognosticate patients with PDAC, we identified 20 genes by utilizing publically available high-throughput transcriptom...
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Published in: | PloS one 2020-04, Vol.15 (4), p.e0231835-e0231835 |
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creator | Demirkol Canlı, Seçil Dedeoğlu, Ege Akbar, Muhammad Waqas Küçükkaraduman, Barış İşbilen, Murat Erdoğan, Özge Şükrüoğlu Erciyas, Seda Kılıç Yazıcı, Hülya Vural, Burçak Güre, Ali Osmay |
description | Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers. Known risk factors for this disease are currently insufficient in predicting mortality. In order to better prognosticate patients with PDAC, we identified 20 genes by utilizing publically available high-throughput transcriptomic data from GEO, TCGA and ICGC which are associated with overall survival and event-free survival. A score generated based on the expression matrix of these genes was validated in two independent cohorts. We find that this "Pancreatic cancer prognostic score 20 -PPS20" is independent of the confounding factors in multivariate analyses, is dramatically elevated in metastatic tissue compared to primary tumor, and is higher in primary tumors compared to normal pancreatic tissue. Transcriptomic analyses show that tumors with low PPS20 have overall more immune cell infiltration and a higher CD8 T cell/Treg ratio when compared to those with high PPS20. Analyses of proteomic data from TCGA PAAD indicated higher levels of Cyclin B1, RAD51, EGFR and a lower E-cadherin/Fibronectin ratio in tumors with high PPS20. The PPS20 score defines not only prognostic and biological sub-groups but can predict response to targeted therapy as well. Overall, PPS20 is a stronger and more robust transcriptomic signature when compared to similar, previously published gene lists. |
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Known risk factors for this disease are currently insufficient in predicting mortality. In order to better prognosticate patients with PDAC, we identified 20 genes by utilizing publically available high-throughput transcriptomic data from GEO, TCGA and ICGC which are associated with overall survival and event-free survival. A score generated based on the expression matrix of these genes was validated in two independent cohorts. We find that this "Pancreatic cancer prognostic score 20 -PPS20" is independent of the confounding factors in multivariate analyses, is dramatically elevated in metastatic tissue compared to primary tumor, and is higher in primary tumors compared to normal pancreatic tissue. Transcriptomic analyses show that tumors with low PPS20 have overall more immune cell infiltration and a higher CD8 T cell/Treg ratio when compared to those with high PPS20. Analyses of proteomic data from TCGA PAAD indicated higher levels of Cyclin B1, RAD51, EGFR and a lower E-cadherin/Fibronectin ratio in tumors with high PPS20. The PPS20 score defines not only prognostic and biological sub-groups but can predict response to targeted therapy as well. Overall, PPS20 is a stronger and more robust transcriptomic signature when compared to similar, previously published gene lists.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0231835</identifier><identifier>PMID: 32310997</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adenocarcinoma ; Biology and Life Sciences ; Cancer therapies ; CD8 antigen ; Cyclin B1 ; Cytotoxicity ; Datasets ; E-cadherin ; Epidermal growth factor receptors ; Fibronectin ; Gene expression ; Genes ; Health risks ; Immune system ; Lymphocytes ; Lymphocytes T ; Medical prognosis ; Medicine and Health Sciences ; Metastases ; Molecular biology ; Oncology ; Pancreatic cancer ; Proteomics ; Risk analysis ; Risk factors ; Survival ; Tissue analysis ; Tumors</subject><ispartof>PloS one, 2020-04, Vol.15 (4), p.e0231835-e0231835</ispartof><rights>2020 Demirkol Canlı et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 Demirkol Canlı et al 2020 Demirkol Canlı et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-d60e5d7ab8d35584083cda262fbcbb8ade3d40f45c807763fb0f420568d7f2383</citedby><cites>FETCH-LOGICAL-c526t-d60e5d7ab8d35584083cda262fbcbb8ade3d40f45c807763fb0f420568d7f2383</cites><orcidid>0000-0003-4417-4005 ; 0000-0003-0200-7962</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2392432592/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2392432592?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32310997$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Silvestris, Nicola</contributor><creatorcontrib>Demirkol Canlı, Seçil</creatorcontrib><creatorcontrib>Dedeoğlu, Ege</creatorcontrib><creatorcontrib>Akbar, Muhammad Waqas</creatorcontrib><creatorcontrib>Küçükkaraduman, Barış</creatorcontrib><creatorcontrib>İşbilen, Murat</creatorcontrib><creatorcontrib>Erdoğan, Özge Şükrüoğlu</creatorcontrib><creatorcontrib>Erciyas, Seda Kılıç</creatorcontrib><creatorcontrib>Yazıcı, Hülya</creatorcontrib><creatorcontrib>Vural, Burçak</creatorcontrib><creatorcontrib>Güre, Ali Osmay</creatorcontrib><title>A novel 20-gene prognostic score in pancreatic adenocarcinoma</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers. Known risk factors for this disease are currently insufficient in predicting mortality. In order to better prognosticate patients with PDAC, we identified 20 genes by utilizing publically available high-throughput transcriptomic data from GEO, TCGA and ICGC which are associated with overall survival and event-free survival. A score generated based on the expression matrix of these genes was validated in two independent cohorts. We find that this "Pancreatic cancer prognostic score 20 -PPS20" is independent of the confounding factors in multivariate analyses, is dramatically elevated in metastatic tissue compared to primary tumor, and is higher in primary tumors compared to normal pancreatic tissue. Transcriptomic analyses show that tumors with low PPS20 have overall more immune cell infiltration and a higher CD8 T cell/Treg ratio when compared to those with high PPS20. 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Known risk factors for this disease are currently insufficient in predicting mortality. In order to better prognosticate patients with PDAC, we identified 20 genes by utilizing publically available high-throughput transcriptomic data from GEO, TCGA and ICGC which are associated with overall survival and event-free survival. A score generated based on the expression matrix of these genes was validated in two independent cohorts. We find that this "Pancreatic cancer prognostic score 20 -PPS20" is independent of the confounding factors in multivariate analyses, is dramatically elevated in metastatic tissue compared to primary tumor, and is higher in primary tumors compared to normal pancreatic tissue. Transcriptomic analyses show that tumors with low PPS20 have overall more immune cell infiltration and a higher CD8 T cell/Treg ratio when compared to those with high PPS20. 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subjects | Adenocarcinoma Biology and Life Sciences Cancer therapies CD8 antigen Cyclin B1 Cytotoxicity Datasets E-cadherin Epidermal growth factor receptors Fibronectin Gene expression Genes Health risks Immune system Lymphocytes Lymphocytes T Medical prognosis Medicine and Health Sciences Metastases Molecular biology Oncology Pancreatic cancer Proteomics Risk analysis Risk factors Survival Tissue analysis Tumors |
title | A novel 20-gene prognostic score in pancreatic adenocarcinoma |
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