Background
Early detection of lung squamous cell carcinoma (LUSC) is significantly effective in clinical management. This study aimed to identify potential LUSC biomarkers based on the epigenetic alterations of miRNAs and DNA methylation.
Methods
Analysis of expression profiles in LUSC clinical samples downloaded from The Cancer Genome Atlas (TCGA-LUSC) datasets was performed to identify differentially expressed genes (DEGs) using R packages. The biological functions were annotated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The protein-protein interaction (PPI) network of the DEGs was established through STRING (Search Tool for the Retrieval of Interacting Genes database) website, visualized by Cytoscape and further analyzed by Molecular Complex Detection (MCODE). Kaplan-meier method and univariate Cox proportional risk regression analysis were used to screen differential genes related to survival in LUSC patients. Multivariate Cox proportional risk regression analysis was used to construct a prognosis prediction model of LUSC patients with differentially expressed genes. Receiver operating characteristic (ROC) curve analysis confirmed the biomarker's specific and sensitivity.
Results
We systematically identified 96 DEGs modified by both DNA methylation and miRNA through TCGA dataset between LUSC tissues and normal tissues. KEGG pathway and GO enrichment analysis gave us an insightful view of the functions of DEMs and DMGs. Subsequently, the four-gene prognosis model were obtained, including SMAD7, MEF2C, TCF21, and TRIB1, together with clinical factors, smoking history and EvsA. Survival curve analysis indicates that the model has good predictive value for the prognosis of patients with LUSC. We also found their differential expression, especially MEF2C and TCF21, together with immune infiltration levels in B cells, CD8 + T cells, CD4 + T cells, macrophages, neutrophils, and dendritic cells, correlated with LUSC prognosis.
Conclusions
Four DEGs modified by both DNA methylation and miRNA were associated with the overall survival of LUSC patients and could be potential biomarkers to predict prognosis. MEF2C and TCF21 likely play important roles in immune cell infiltration and as prognosis biomarkers in LUSC patients with immune cell infiltration. In future research, we will explore the prognostic genes and their potential function based on the present study.