IRF4 Correlated With Immune Cells Infiltration Could Predict Prognosis for Patients With Lung Adenocarcinoma

Abstract

Finding prognostic biomarkers and novel targets to optimize immunotherapy for non-small-cell lung carcinoma (NSCLC) is necessary and urgent. Immune related interferon regulatory factor 4 (IRF4) is a member of the IRF family, whereas the clinical significance and possible role of IRF4 in NSCLC remains unclear.We analyzed the expression levels of IRF4 via Oncomine and Tumor Immune Estimation Resource (TIMER) databases. Additionally, we assessed the correlation between IRF4 and overall survival in Lung adenocarcinoma (LUAD) and Lung squamous cell carcinoma (LUSC) using the Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan Meier plotter databases. We also used the TIMER and TISIDB databases to analyze the correlation between IRF4 expression and immune infiltration level. We further carried out a survival analysis between IRF4 and LUAD based on immune cellular content. Using the UALCAN database, we analyzed the relationship between IRF4 and LUAD with different clinical features.IRF4 was significantly overexpressed in LUAD compared to normal tissues, and high IRF4 predicted better survival in LUAD patients. However, our results showed that IRF4 was not correlated the survival of LUSC patients. Using TIMER and TISIDB databases, we demonstrated that IRF4 was positively correlated with various immune infiltrations including B Cells, CD8+ T Cells, CD4+ T Cells, Neutrophil and Dendritic Cells in both LUAD and LUSC. Additionally, we found that the prognostic value of IRF4 diminished in LUAD with decreasing levels of B cells, but not other immune cellular contents. Correspondingly, we found that the prognostic ability of tumor-infiltrating B lymphocyte (TIL-B) in LUAD was depended on the contribution of high IRF4 expression. Besides, we found that IRF4 expression level was significantly higher in the early stage of LUAD compared to advanced stage.Our results suggested that IRF4 is associated with higher immune infiltration levels especially for TIL-B and is a potential favorable prognostic biomarker in LUAD.