Immune-Related RNA-Binding Protein-Based Signature With Predictive and Prognostic Implications in Patients With Lung Adenocarcinoma.

Dysregulation of RNA-binding proteins (RBPs) in cancers is associated with immune and cancer development. Here, we aimed to profile immune-related RBPs in lung adenocarcinoma (LUAD) and construct an immune-related RBP signature (IRBPS) to predict the survival and response to immunotherapy. A correlation analysis was performed to establish a co-expression network of RBPs and immune-related genes (IRGs) to characterize immune-related RBPs in the TCGA-LUAD cohort ( = 497 cases). Then, a combination of the Random survival forest (RSF) and Cox regression analysis was performed to screen the RBPs and establish IRBPS. This was followed by independent validation of IRBPS in GSE72094 ( = 398 cases), GSE31210, ( = 226 cases), and GSE26939 ( = 114 cases). Differences between the low- and high-risk groups were compared in terms of gene mutations, tumor mutation burden, tumor-infiltrating lymphocytes, and biomarkers responsive to immunotherapy. DDX56, CTSL, ZC3H12D, and PSMC5 were selected and used to construct IRBPS. The high-risk scores of patients had a significantly worse prognosis in both training and testing cohorts ( < 0.0001 and < 0.05, respectively), and they tended to be older and have an advanced TNM stage. Furthermore, IRBPS was a prognostic factor independent of age, gender, smoking history, TNM stage, and EGFR mutation status ( = 0.002). In addition, high-risk scores of IRBPS were significantly correlated with tumor-infiltrating lymphocytes ( < 0.05). They also had a high level of PD-L1 protein expression ( < 0.01), number of neoantigens ( < 0.001), and TMB ( < 0.001), implying the possible prediction of IRBPS in the immunotherapy of LUAD. The currently established IRBPS encompassing immune-related RBPs might serve as a promising tool to predict survival, reflect the immune microenvironment, and predict the efficacy of immunotherapy among LUAD patients.