The construction and analysis of ceRNA network and patterns of immune infiltration in lung adenocarcinoma

Abstract

Background: Competitive Endogenous RNA (ceRNA) may be closely associated with tumor progression. However, studies on ceRNAs and immune cells in LUAD are scarce.

Method: The profiles of gene expression and clinical data of LUAD patients were extracted from the TCGA database. Bioinformatics methods were used to evaluate differentially-expressed genes (DEGs) and to form a ceRNA network. Preliminary verification of clinical specimens was utilized to detect the expressions of key biomarkers at the tissues. Cox and Lasso regressions were used to identify key genes, and prognosis prediction nomograms were formed. The mRNA levels of 9 genes in the risk score model in independent clinical LUAD samples were detected by qRT-PCR. The interconnection between the risk of cancer and immune cells was evaluated using the CIBERSORT algorithm, while the conformation of notable tumor-infiltrating immune cells (TIICs) in the LUAD tissues of the high and low risk groups was assessed using the RNA transcript subgroup in order to identify tissue types. Finally, co-expression study was used to examine the interconnection between the key genes in the ceRNA networks and the immune cells.

Result: A ceRNA network of 115 RNAs was established, and nine key genes were identified to construct a Cox proportional-hazard model and create a prognostic nomogram. This risk-assessment model might serve as an independent factor to forecast the prognosis of LUAD, and it was consistent with the preliminary verification of clinical specimens. Survival analysis of clinical samples further validated the potential value of high risk groups in predicting LUAD prognosis. Five immune cells were identified with significant differences in the LUAD tissues of the high and low risk groups. Besides, two pairs of biomarkers associated with the growth of LUAD were found, i.e., E2F7 and macrophage M1 (R = 0.419, p = 1.4e^{- 08}) and DBF4 and macrophage M1 (R = 0.282, p < 2.2 e^{- 16}).

Conclusion: This study identified several important ceRNAs, i.e. (E2F7 and BNF4) and TIICs (macrophage M1), which might be related to the development and prognosis of LUAD. The established risk-assessment model might be a potential tool in predicting LUAD of prognosis.

Keywords: Competitive endogenous RNA (ceRNA); Lung adenocarcinoma (LUAD); MicroRNA; Risk-assessment model; Tumor-infiltrating immune cells (TIICs).