A nomogram based on A-to-I RNA editing predicting overall survival of patients with lung squamous carcinoma

Abstract

Background Adenosine-to-inosine RNA editing (ATIRE) is characterized as non-mutational epigenetic reprogramming hallmark of cancer, while little is known about its predictive role in cancer survival. Methods To explore survival-related ATIRE events in lung squamous cell carcinoma (LUSC), ATIRE profile, gene expression data, and corresponding clinical information of LUSC patients were downloaded from the TCGA database. Patients were randomly divided into a training (n = 134) and validation cohort (n = 94). Cox proportional hazards regression followed by least absolute shrinkage and selection operator algorithm were performed to identify survival-related ATIRE sites and to generate ATIRE risk score. Then a nomogram was constructed to predict overall survival (OS) of LUSC patients. The correlation of ATIRE level and host gene expression and ATIREs’ effect on transcriptome expression were analyzed. Results Seven ATIRE sites that were TMEM120B chr12:122215052A > I, HMOX2 chr16:4533713A > I, CALCOCO2 chr17:46941503A > I, LONP2 chr16:48388244A > I, ZNF440 chr19:11945758A > I, CLCC1 chr1:109474650A > I, and CHMP3 chr2:86754288A > I were identified to generate the risk score, of which high levers were significantly associated with worse OS and progression-free survival in both the training and validation sets. High risk-score was also associated with advanced T stages and worse clinical stages. The nomogram performed well in predicting OS probability of LUSC. Moreover, the editing of ATIRE sites exerted a significant association with expression of host genes and affected several cancer-related pathways. Conclusions This is the first comprehensive study to analyze the role of ATIRE events in predicting LUSC survival. The AITRE-based model might serve as a novel tool for LUSC survival prediction.

Clinical relevance of RNA editing profiles in lung adenocarcinoma

“…However, further research is necessary to determine the exact mechanism of these editing sites. TMEM120B, HMOX2, CALCOCO2, LONP2, ZNF440, CLCC1, and CHMP3 were identified to be optimal prognostic factors for lung squamous cell carcinoma (LUSC) ( Liu et al, 2022a ). In multivariate Cox regression analysis, PGPEP1 chr19:18476416A > I, ANKRD36BP1 (dist = 3,795), TBX19 (dist = 29815) chr1:168220463A > I, SNTB2 chr16:69338598A > I, HOOK3 chr8:42883441A > I, NDUFV3 chr21:44329452A > I, and FKBP11 chr12:49316769A > I were prognostic ATIRE sites of LUAD patients.…”