Distinct Expression Pattern and Prognostic Values of E2F Family Genes in Lung Adenocarcinoma and Squamous Cell Carcinoma

The E2F transcription factors family included E2F1-8 playing the crucial roles in the origination and progression of various kinds of human cancers. However, a comprehensive analysis regarding the gene mRNA expression pattern at bulk and single-cell resolution, the prognostic values and the association to immune cell infiltration of E2F family genes in lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) remains to be performed. The bulk and single-cell mRNA expression levels of E2F family members in LUAD and LUSC were determined using the cBioPortal, Gepia, TISCH and Oncomine online databases. Based on the differentially expressed genes, GO enrichment and GSEA items were investigated. The Kaplan‑Meier plotter server was used to evaluate the prognostic significances of the E2F family genes in patients with LUAD and LUSC based on the related clinicopathological features. The correlation between E2F family gene expression and immune cell infiltration was explored using the Timer database. Our bulk and single-cell RNA analyses revealed that E2F1, E2F2 and E2F8 might promote the tumor growth and aggressiveness of LUAD and LUSC indicating the poor prognosis prediction. E2F4 and E2F6 might be considered as the potential outcome markers for the improved treatment of LUAD and LUSC, respectively. Upregulation of E2F1 and E2F8 indicated the poor prognosis of LUAD patients, whereas only E2F2 overexpression was associated with shorter overall survival of LUSC patients. There existed a positive relationship between E2F8 expression level and infiltration level of macrophages and DCs, and significantly positive correlation between infiltration level of CD8+ T, CD4+ T cells and E2F1/2/7 expression in LUAD and LUSC. In conclusion, our findings suggested that increased expression of E2F1/E2F8 or E2F2 may serve as promising prognostic biomarkers for patients with LUAD or LUSC, respectively.