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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
Main Authors: 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
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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. 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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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