Identification of Potential Prognostic Biomarkers Associated with Monocyte Infiltration in Lung Squamous Cell Carcinoma

Abstract

The five-year survival rate of lung squamous cell carcinoma is significantly lower than that of other cancer types. It is therefore urgent to discover novel prognosis biomarkers and therapeutic targets and understand their correction with infiltrating immune cells to improve the prognosis of patients with lung squamous cell carcinoma. In this study, we employed robust rank aggregation algorithms to overcome the shortcomings of small sizes and potential bias in each Gene Expression Omnibus dataset of lung squamous cell carcinoma and identified 513 robust differentially expressed genes including 220 upregulated and 293 downregulated genes from six microarray datasets. Functional enrichment analysis showed that these robust differentially expressed genes were obviously involved in the extracellular matrix and structure organization, epidermis development, cell adhesion molecule binding, p53 signaling pathway, and interleukin-17 signaling pathway to affect the progress of lung squamous cell carcinoma. We further identified six hub genes from 513 robust differentially expressed genes by protein-protein interaction network and 10 topological analyses. Moreover, the results of immune cell infiltration analysis from six integrated Gene Expression Omnibus datasets and our sequencing transcriptome data demonstrated that the abundance of monocytes was significantly lower in lung squamous cell carcinoma compared to controls. Immune correlation analysis and survival analysis of hub genes suggested that three hub genes, collagen alpha-1(VII) chain, mesothelin, and chordin-like protein 1, significantly correlated with tumor-infiltrating monocytes as well as may be potential prognostic biomarkers and therapy targets in lung squamous cell carcinoma. The investigation of the correlation of hub gene markers and infiltrating monocytes can also improve to well understand the molecular mechanisms of lung squamous cell carcinoma development.