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

Bibliographic Details
Title: Development and Validation of a Four Adenosine-to-Inosine RNA Editing Site-Relevant Prognostic Signature for Assessing Survival in Breast Cancer Patients
Authors: Jian Wan, Shizhen Chen, Anqin Zhang, Yiting Liu, Yangyang Zhang, Qinghua Li, Ziqi Yu, Yuwei Wan, Lei Yang, Qi Wang
Source: Frontiers in Oncology, Vol 12 (2022)
Publisher Information: Frontiers Media S.A., 2022.
Publication Year: 2022
Collection: LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Subject Terms: A-to-I RNA editing, breast cancer, nomogram, overall survival, disease-free survival, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
More Details: 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.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2234-943X
Relation: https://www.frontiersin.org/articles/10.3389/fonc.2022.861439/full; https://doaj.org/toc/2234-943X
DOI: 10.3389/fonc.2022.861439
Access URL: https://doaj.org/article/d53b057b88c64725886fd4d6793deb68
Accession Number: edsdoj.53b057b88c64725886fd4d6793deb68
Database: Directory of Open Access Journals
More Details
ISSN:2234943X
DOI:10.3389/fonc.2022.861439
Published in:Frontiers in Oncology
Language:English