AUTHOR=Xu Lei , Li Wanru , Yang Ting , Hu Siqi , Zou Qiong , Jiao Ju , Jiang Ningyi , Zhang Yong 

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

JOURNAL=Frontiers in Molecular Biosciences

VOLUME=9

YEAR=2022

URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2022.807622

DOI=10.3389/fmolb.2022.807622

ISSN=2296-889X

ABSTRACT=<p><bold>Background:</bold> 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.</p><p><bold>Methods:</bold> 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 (<italic>n</italic> = 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 (<italic>n</italic> = 398 cases), GSE31210, (<italic>n</italic> = 226 cases), and GSE26939 (<italic>n</italic> = 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.</p><p><bold>Results:</bold> 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 (<italic>p</italic> &lt; 0.0001 and <italic>p</italic> &lt; 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 (<italic>p</italic> = 0.002). In addition, high-risk scores of IRBPS were significantly correlated with tumor-infiltrating lymphocytes (<italic>p</italic> &lt; 0.05). They also had a high level of PD-L1 protein expression (<italic>p</italic> &lt; 0.01), number of neoantigens (<italic>p</italic> &lt; 0.001), and TMB (<italic>p</italic> &lt; 0.001), implying the possible prediction of IRBPS in the immunotherapy of LUAD.</p><p><bold>Conclusion:</bold> 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.</p>