A novel adenosine-to-inosine RNA editing-based nomogram for predicting prognosis of hepatocellular carcinoma

Objective: Although the role of adenosine-to-inosine RNA editing (ATIRE) has gained widespread attention in multiple cancers, its predictive role in hepatocellular carcinoma (HCC) remains little known. We aimed to establish a predicting signature based on ATIRE for the prognosis of HCC. Methods: A total of 200 HCC patients with survival data and ATIRE profiles from The Cancer Genome Atlas (TCGA) database were divided into training (n = 140) and validation (n = 60) cohorts. Survival-related ATIRE sites were identified by the least absolute shrinkage and selection operator algorithm. ATIRE-based risk score was then generated with these ATIRE sites. Cox proportional hazards regression was employed to construct the ATIRE-based nomogram signature. The receiver operating characteristic (ROC) curve was used to evaluate the predictive efficacy of the signature. Harrell’s C-index and calibration plot was utilized to evaluate the significant prognostic factors. Results: Nine ATIRE sites were screened to establish the ATIRE risk score, and it was found to be associated with prognosis of HCC. Survival analysis revealed that higher ATIRE-based risk scores were significantly associated with worse overall survival (OS) in both the training dataset ( p < 0.001) and the validation dataset ( p = 0.011), as well as in the combined dataset ( p < 0.001). The ROC curve displayed a good predictive efficiency of the risk score regarding 1-year, 2-year, and 3-year OS. Furthermore, ATIRE sites were significantly correlated with the expression of host genes and were likely to be involved in certain cancer-related pathways. Discussion: Our findings provided a novel ATIRE-based nomogram, which could serve as a potential tool for predicting HCC prognosis.