Construction and Characterization of Long Non-Coding RNA-Associated Networks to Reveal Potential Prognostic Biomarkers in Human Lung Adenocarcinoma

Abstract

Lung adenocarcinoma (LUAD) is one type of the malignant tumors with high morbidity and mortality. The molecular mechanism of LUAD is still unclear. Studies demonstrate that lncRNAs play crucial roles in LUAD tumorigenesis and can be used as prognosis biomarkers. Thus, in this study, to identify more robust biomarkers of LUAD, we firstly constructed LUAD-related lncRNA-TF network and performed topological analyses for the network. Results showed that the network was a scale-free network, and some hub genes with high clinical values were identified, such as lncRNA RP11-173A16 and TF ZBTB37. Module analysis on the network revealed one close lncRNA module, which had good prognosis performance in LUAD. Furthermore, through integrating ceRNAs strategy and TF regulatory information, we identified some lncRNA-TF positive feedback loops. Prognostic analysis revealed that ELK4- and BDP1-related feedback loops were significant. Secondly, we constructed the lncRNA-m6A regulator network by merging all the high correlated lncRNA-m6A regulator pairs. Based on the network analysis results, some key m6A-related lncRNAs were identified, such as MIR497HG, FENDRR, and RP1-199J3. We also investigated the relationships between these lncRNAs and immune cell infiltration. Results showed that these m6A-related lncRNAs were high correlated with tumor immunity. All these results provide a new perspective for the diagnostic biomarker and therapeutic target identification of LUAD.