Objectives Lung squamous cell carcinoma (LUSC) often diagnosed as advanced with poor prognosis. The mechanisms of its pathogenesis and prognosis require urgent elucidation. This study was performed to screen potential biomarkers related to the occurrence, development and prognosis of LUSC to reveal unknown physiological and pathological processes. Materials and Methods Using bioinformatics analysis, the lung squamous cell carcinoma microarray datasets from the GEO and TCGA databases were analyzed to identify differentially expressed genes(DEGs). Furthermore, PPI and WGCNA network analysis were integrated to identify the key genes closely related to the process of LUSC development. In addition, survival analysis was performed to achieve a prognostic model that accomplished a high level of prediction accuracy. Results and Conclusion Eighty-five up-regulated and 39 down-regulated genes were identified, on which functional and pathway enrichment analysis was conducted. GO analysis demonstrated that up-regulated genes were principally enriched in epidermal development and DNA unwinding in DNA replication. Down-regulated genes were mainly involved in cell adhesion, signal transduction and positive regulation of inflammatory response. After PPI and WGCNA network analysis, eight genes, including AURKA, RAD51, TTK, AURKB, CCNA2, TPX2, KPNA2 and KIF23, have been found to play a vital role in LUSC development. The prognostic model contained 20 genes, 18 of which were detrimental to prognosis. The AUC of the established prognostic model for predicting the survival of patients at 1, 3, and 5 years was 0.828, 0.826 and 0.824, respectively. To conclude, this study identified a number of biomarkers of significant interest for additional investigation of the therapies and methods of prognosis of lung squamous cell carcinoma.
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