A Nomogram Based On A-To-I RNA Editing Predicting The Overall Survival of Patients With Lung Squamous Carcinoma

Abstract Background: A-to-I RNA editing has been recognized as a novel hallmark of cancer, while little is known about its contribution to cancer prognosis. We aimed to develop a prognostic nomogram with A-to-I editing events in lung squamous cell carcinoma (LUSC). Methods: The TCGA A-to-I editing profile, corresponding clinical and gene expression data of LUSC were analyzed. Patients were randomly divided into a training (n = 134) and validation group (n = 94). An A-to-I risk biosignature was generated by univariate Cox regression and followed Lasso regression. Results: We identified a seven A-to-I sites-based risk biosignature that includes TMEM120B(A2588I), HMOX2(A224I), CALCOCO2(A2603I), MIR548AE2(A113641I), ZNF440(A3942I), CLCC1(A2315I), and CHMP3(A23735I). High risk was significantly associated with worse overall survival (OS) in both the training (HR = 7.30; 95%CI = 3.48-15.3) and validation groups (HR = 2.13; 95%CI = 1.09-4.15). Patients with advanced T (P = 0.021) or clinical stages (P = 0.021) had higher risk scores than the counterparters. We then developed a nomogram incorporating the A-to-I biosignature and clinicopathological features, which exerted well performance on predicting probability of LUSC OS with C-indexes as 0.808 and 0.685 in both sets. Moreover, the editing levels of ZNF440(A3942I), CLCC1(A2315I), HMOX2(A224I) are correlated with expressions of their host genes, while the levels of TMEM120B(A2588I), CLCC1(A2315I), and CALCOCO2(A2603I) differed between tumor tissues and normal tissues. Conclusions: Our results for the first time provided insight into the development of A-to-I editing‑based nomogram for predicting OS of LUSC patients.