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

ABSTRACT:

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 signatures 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?ConclusionTwo pan-cancer prognostic signatures of oxygen-sensing genes were identified. These genes can be used for risk stratification in ten diverse cancer types to reveal aggressive tumor subtypes.

SUBMITTER: Chang WH 

PROVIDER: S-EPMC6489267 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature