Construction and Analysis of lncRNA-Mediated ceRNA Network in Nasopharyngeal Carcinoma Based on Weighted Correlation Network Analysis

Abstract EN

Increasing evidence indicated that aberrant expression of long noncoding RNAs (lncRNAs) are involved in tumorigenesis of nasopharyngeal carcinoma (NPC).

The purpose of this study was to construct a lncRNA-mediated ceRNA network based on weighted correlation network analysis (WGCNA).

First, modules with highly correlated genes were identified from GSE102349 via WGCNA, and the preservation of the modules was evaluated by GSE68799.

Then, the differentially expressed lncRNAs and mRNAs identified from GSE12452 which belonged to the same WGCNA modules and the differentially expressed miRNAs identified from GSE32960 were used to construct a ceRNA network.

The prognostic value of the network was evaluated by survival analysis.

Furthermore, a risk score model for predicting progression-free survival (PFS) of NPC patients was established via LASSO-penalized Cox regression, and the differences in the expression of the lncRNAs between high- and low-risk groups were investigated.

Finally, 14 stable modules were identified, and a ceRNA network composed of 11 lncRNAs, 15 miRNAs, and 40 mRNAs was established.

The lncRNAs and mRNAs in the network belonged to the turquoise and salmon modules.

Survival analysis indicated that ZNF667-AS1, LDHA, LMNB2, TPI1, UNG, and hsa-miR-142-3p were significantly correlated with the prognosis of NPC.

Gene set enrichment analysis indicated that the upregulation of ZNF667-AS1 was associated with some immune-related pathways.

Besides, a risk score model consisting of 12 genes was constructed and showed a good performance in predicting PFS for NPC patients.

Among the 11 lncRNAs in the ceRNA network, SNHG16, SNHG17, and THAP9-AS1 were upregulated in the high-risk group of NPC, while ZNF667-AS1 was downregulated in the high-risk group of NPC.

These results will promote our understanding of the crosstalk among lncRNAs, miRNAs, and mRNAs in the tumorigenesis and progression of NPC.