Systematic analysis identifies three-lncRNA signature as a potentially prognostic biomarker for lung squamous cell carcinoma using bioinformatics strategy

Jing Hu, Lutong Xu, Tao Shou, Qiang Chen


Background: Lung squamous cell carcinoma (LUSC) is the second most common histological subtype of lung cancer (LC), and the prognoses of most LUSC patients are so far still very poor. The present study aimed at integrating lncRNA, miRNA and mRNA expression data to identify lncRNA signature in competitive endogenous RNA (ceRNA) network as a potentially prognostic biomarker for LUSC patients.
Methods: Gene expression data and clinical characteristics of LUSC patients were retrieved from The Cancer Genome Atlas (TCGA) database, and were integratedly analyzed using bioinformatics methods including Differentially Expressed Gene Analysis (DEGA), Weighted Gene Co-expression Network Analysis (WGCNA), Protein and Protein Interaction (PPI) network analysis and ceRNA network construction. Subsequently, univariate and multivariate Cox regression analyses of differentially expressed lncRNAs (DElncRNAs) in ceRNA network were performed to predict the overall survival (OS) in LUSC patients. Receiver operating characteristic (ROC) analysis was used to evaluate the performance of multivariate Cox regression model. Gene expression profiling interactive analysis (GEPIA) was used to validate key genes.
Results: WGCNA showed that turquoise module including 1,694 DElncRNAs, 2,654 DEmRNAs as well as 113 DEmiRNAs was identified as the most significant modules (cor=0.99, P<1e-200), and differentially expressed RNAs in the module were used to subsequently analyze. PPI network analysis identified FPR2, GNG11 and ADCY4 as critical genes in LUSC, and survival analysis revealed that low mRNA expression of FPR2 and GNG11 resulted in a higher OS rate of LUSC patients. A lncRNA-miRNA-mRNA ceRNA network including 121 DElncRNAs, 18 DEmiRNAs and 3 DEmRNAs was established, and univariate and multivariate Cox regression analysis of those 121 DElncRNAs showed a group of 3 DElncRNAs (TTTY16, POU6F2-AS2 and CACNA2D3-AS1) had significantly prognostic value in OS of LUSC patients. ROC analysis showed that the area under the curve (AUC) of the 3-lncRNA signature associated with 3-year survival was 0.629.
Conclusions: The current study provides novel insights into the lncRNA-related regulatory mechanisms underlying LUSC, and identifying 3-lncRNA signature may serve as a potentially prognostic biomarker in predicting the OS of LUSC patients.