Dual prognostic role of 2-oxoglutarate-dependent oxygenases in ten cancer types:implications for cell cycle regulation and cell adhesion maintenance  

作　　者：Wai Hoong Chang Donall Forde Alvina G.Lai 

机构地区：[1]Nuffield Department of Medicine,University of Oxford,Old Road Campus,Oxford OX37FZ,UK

出　　处：《Cancer Communications》2019年第1期214-227,共14页癌症通讯（英文）

摘　　要：Background: Tumor hypoxia is associated with metastasis and resistance to chemotherapy and radiotherapy. Genes involved in oxygen-sensing are clinically relevant and have significant implications for prognosis. In this study, we examined the pan-cancer prognostic significance of oxygen-sensing genes from the 2-oxoglutarate-dependent oxygenase family. Methods: A multi-cohort, retrospective study of transcriptional profiles of 20,752 samples of 25 types of cancer was performed to identify pan-cancer prognostic signatures of 2-oxoglutarate-dependent oxygenase gene family (a family of oxygen-dependent enzymes consisting of 61 genes). We defined minimal prognostic gene sets using three independent pancreatic cancer cohorts (n = 681). We identified two signatures, each consisting of 5 genes. The ability of the signa-tures in predicting survival was tested using Cox regression and receiver operating characteristic (ROC) curve analyses. Results: Signature 1 (KDM8, KDM6B, P4HTM, ALKBH4, ALKBH7) and signature 2 (KDM3A, P4HA1, ASPH, PLOD1, PLOD2) were associated with good and poor prognosis. Signature 1 was prognostic in 8 cohorts representing 6 cancer types (n = 2627): bladder urothelial carcinoma (P = 0.039), renal papillary cell carcinoma (P = 0.013), liver cancer (P = 0.033 and P = 0.025), lung adenocarcinoma (P = 0.014), pancreatic adenocarcinoma (P < 0.001 and P = 0.040), and uterine corpus endometrial carcinoma (P < 0.001). Signature 2 was prognostic in 12 cohorts representing 9 cancer types (n = 4134): bladder urothelial carcinoma (P = 0.039), cervical squamous cell carcinoma and endocervical adenocar-cinoma (P = 0.035), head and neck squamous cell carcinoma (P = 0.038), renal clear cell carcinoma (P = 0.012), renal papillary cell carcinoma (P = 0.002), liver cancer (P < 0.001, P < 0.001), lung adenocarcinoma (P = 0.011), pancreatic adenocarcinoma (P = 0.002, P = 0.018, P < 0.001), and gastric adenocarcinoma (P = 0.004). Multivariate Cox regression confirmed independent clinical relevance of the signatures in these

关 键 词：Oxygen-sensing gene 2-Oxoglutarate-dependent oxygenase Pan-cancer Prognosis Hypoxia KDM8 HNF4A 

分 类 号：R73[医药卫生—肿瘤]