RNA editing affects cis-regulatory elements and predicts adverse cancer survival

Abstract

Background: RNA editing exerts critical impacts on numerous biological processes and thus are implicated in crucial human phenotypes, including tumorigenesis and prognosis. While previous studies have analyzed aggregate RNA editing activity at the sample level and associated it with overall cancer survival, there is not yet a large-scale disease-specific survival study to examine genome-wide RNA editing sites’ prognostic value taking into account the host gene expression and clinical variables. Methods: In this study, we solved comprehensive Cox proportional models of disease-specific survival on individual RNA-editing sites plus host gene expression and critical demographic covariates. This allowed us to interrogate the prognostic value of a large number of RNA-editing sites at single-nucleotide resolution. Results: As a result, we identified 402 gene-proximal RNA-editing sites that generally predict adverse cancer survival. For example, an RNA-editing site residing in ZNF264 indicates poor survival of uterine corpus endometrial carcinoma, with a hazard ratio of 2.13 and an adjusted p-value of 4.07 × 10−7. Some of these prognostic RNA-editing sites mediate the binding of RNA binding proteins and microRNAs, thus propagating their impacts to extensive regulatory targets. Conclusions: In conclusion, RNA editing affects cis-regulatory elements and predicts adverse cancer survival.