Identification of a ceRNA Network in Lung Adenocarcinoma Based on Integration Analysis of Tumor-Associated Macrophage Signature Genes

Abstract

As research into tumor-immune interactions progresses, immunotherapy is becoming the most promising treatment against cancers. The tumor microenvironment (TME) plays the key role influencing the efficacy of anti-tumor immunotherapy, in which tumor-associated macrophages (TAMs) are the most important component. Although evidences have emerged revealing that competing endogenous RNAs (ceRNAs) were involved in infiltration, differentiation and function of immune cells by regulating interactions among different varieties of RNAs, limited comprehensive investigation focused on the regulatory mechanism between ceRNA networks and TAMs. In this study, we aimed to utilize bioinformatic approaches to explore how TAMs potentially influence the prognosis and immunotherapy of lung adenocarcinoma (LUAD) patients. Firstly, according to TAM signature genes, we constructed a TAM prognostic risk model by the least absolute shrinkage and selection operator (LASSO) cox regression in LUAD patients. Then, differential gene expression was analyzed between high- and low-risk patients. Weighted gene correlation network analysis (WGCNA) was utilized to identify relevant gene modules correlated with clinical characteristics and prognostic risk score. Moreover, ceRNA networks were built up based on predicting regulatory pairs in differentially expressed genes. Ultimately, by synthesizing information of protein-protein interactions (PPI) analysis and survival analysis, we have successfully identified a core regulatory axis: LINC00324/miR-9-5p (miR-33b-5p)/GAB3 (IKZF1) which may play a pivotal role in regulating TAM risk and prognosis in LUAD patients. The present study contributes to a better understanding of TAMs associated immunosuppression in the TME and provides novel targets and regulatory pathway for anti-tumor immunotherapy.