Development and Validation of a Four Adenosine-to-Inosine RNA Editing Site-Relevant Prognostic Signature for Assessing Survival in Breast Cancer Patients

Frontiers in Oncology

Yiting Liu¹  Jian Wan¹  Anqin Zhang¹  Qi Wang¹  Yangyang Zhang¹  Qinghua Li¹  Ziqi Yu³  Shizhen Chen³  Yuwei Wan³  Lei Yang³ 

[1] Breast Disease Center, Guangdong Women and Children Hospital, Guangzhou, China;The First Affiliated Hospital, Jinan University, Guangzhou, China;The State Key Lab of Respiratory Disease, Institute of Public Health, Guangzhou Medical University, Guangzhou, China;

关键词: A-to-I RNA editing;    breast cancer;    nomogram;    overall survival;    disease-free survival;   

DOI  :  10.3389/fonc.2022.861439

来源: DOAJ

【 摘 要 】

BackgroundAdenosine-to-inosine RNA editing (ATIRE) is increasingly being used to characterize cancer. However, no studies have been conducted to identify an ATIRE signature for predicting cancer survival.MethodsBreast cancer (BRCA) samples with ATIRE profiles from The Cancer Genome Atlas were divided into training (n = 452) and internal validation cohorts (n = 311), and 197 additional BRCA patients were recruited as an external validation cohort. The ATIRE signature for BRCA overall survival (OS) and disease-free survival (DFS) were identified using forest algorithm analysis and experimentally verified by direct sequencing. An ATIRE-based risk score (AIRS) was established with these selected ATIRE sites. Significantly prognostic factors were incorporated to generate a nomogram that was evaluated using Harrell’s C-index and calibration plot for all cohorts.ResultsSeven ATIRE sites were revealed to be associated with both BRCA OS and DFS, of which four sites were experimentally confirmed. Patients with high AIRS displayed a higher risk of death than those with low AIRS in the training (hazard ratio (HR) = 3.142, 95%CI = 1.932–5.111), internal validation (HR = 2.097, 95%CI = 1.123–3.914), and external validation cohorts (HR = 2.680, 95%CI = 1.000–7.194). A similar hazard effect of high AIRS on DFS was also observed. The nomogram yielded Harrell’s C-indexes of 0.816 (95%CI = 0.784–0.847), 0.742 (95%CI = 0.684–0.799), and 0.869 (95%CI = 0.835–0.902) for predicting OS and 0.767 (95%CI = 0.708–0.826), 0.684 (95%CI = 0.605–0.763), and 0.635 (95%CI = 0.566–0.705) for predicting DFS in the three cohorts.ConclusionAIRS nomogram could help to predict OS and DFS of patients with BRCA.

【 授权许可】

Unknown