A novel 20-gene prognostic score in pancreatic adenocarcinoma

Autor: Secil Demirkol Canli, Ozge Sukruoglu Erdogan, Murat Isbilen, Hulya Yazici, Muhammad Waqas Akbar, Baris Kucukkaraduman, Burçak Vural, Ali O. Gure, Seda Kilic Erciyas, Ege Dedeoğlu
Přispěvatelé: Dedeoğlu, Ege, Akbar, Muhammad Waqas, Küçükkaraduman, Barış, İşbilen, Murat, Güre, Ali Osmay
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Oncology
Cytotoxicity
medicine.medical_treatment
Cancer Treatment
Gene Expression
Toxicology
Pathology and Laboratory Medicine
Targeted therapy
0302 clinical medicine
Animal Cells
Adenocarcinomas
Medicine and Health Sciences
Medicine
Molecular Targeted Therapy
Cyclin B1
Multidisciplinary
Prognosis
Primary tumor
Gene Expression Regulation
Neoplastic
030220 oncology & carcinogenesis
Adenocarcinoma
Cellular Types
Research Article
Carcinoma
Pancreatic Ductal
medicine.medical_specialty
Immune Cells
Science
Immunology
Carcinomas
Pancreatic Cancer
03 medical and health sciences
Diagnostic Medicine
Internal medicine
Pancreatic cancer
Gastrointestinal Tumors
Genetics
Carcinoma
Humans
Survival analysis
Pharmacology
Drug Screening
business.industry
Gene Expression Profiling
Cancers and Neoplasms
Biology and Life Sciences
Cell Biology
medicine.disease
Survival Analysis
Pancreatic Neoplasms
Gene expression profiling
030104 developmental biology
business
Zdroj: PLoS ONE
PLoS ONE, Vol 15, Iss 4, p e0231835 (2020)
Popis: Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers. Known risk factors for this disease are currently insufficient in predicting mortality. The only FDA approved prognostic biomarker for PDAC patients is CA19-9. This, along with AJCC TNM staging and performance status, are considered important prognostic indicators in clinical practice. In order to better prognosticate patients with PDAC, we identified a novel panel of genes by utilizing publically available microarray and RNAseq data of PDAC tumors from GEO and TCGA. Expression of 20 genes were significantly associated with overall survival in four datasets and event-free survival in TCGA. A score generated based on the expression matrix of these genes could be validated in two independent cohorts. We find that this “Pancreatic cancer prognostic score 20 – PPS20” 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 options as well. Overall, PPS20 is a stronger and more robust transcriptomic signature when compared to similar, previously published gene lists.
Databáze: OpenAIRE
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