Abstract
BackgroundIt was demonstrated that multifunctional protein APE1 (Apurinic/apyrimidinic endonuclease 1) is closely related to tumor immune microenvironment in a number of investigations, Meanwhile, the abundance of tumor infiltrating lymphocytes (TILs) has been shown as a prognosis indicator in some researches. However, it remains unclear whether APE1 is involved in the process of TILs affecting the prognosis of patients. To this end, we investigated the associations between APE1 and TILs in non-small cell lung cancer (NSCLC) and explored whether APE1 would influence the associations of CD4+ T cells infiltration with the prognosis of patients.MethodsGenome-wide expression datasets were obtained from the Gene Expression Omnibus (GEO) public database under accession number GSE68465, GSE30219, GSE31210 and GSE50081. MCPcounter and CIBERSORT analysis was conducted to evaluate the abundance of TILs in 1006 NSCLC patients of GEO database. Spearman correlation tests were used to evaluate correlations between abundance of various TILs and APE1 expression. RFS (recurrence free survival) was estimated using the Kaplan–Meier method and the Cox proportional-hazards model. The expression level of APE1 and tumor-infiltrating CD4+ T cells was evaluated by immunohistochemistry (IHC).ResultsThe results showed that the abundance of CD4+ naïve T cells was negatively associated with the APE1 expression. CD4+ naïve T cells infiltration was a favorable prognostic factor for RFS, however, there was no effect of CD4+ T cells infiltration on RFS in patients with high APE1 expression. Subsequently, it was further confirmed that CD4+ T cells infiltration was negatively associated with the APE1 expression level in 108 NSCLC tissue samples; high CD4+ T cells infiltration was associated with longer RFS in low APE1 expression group but not in APE1 high expression group.ConclusionThese results suggested that APE1 may affect the relationship between CD4+ T cells infiltration and prognosis in NSCLC. This study provides new insights into predictors of outcome in patients with NSCLC, and suggests that combining immunotherapy and APE1-targeted therapy may be a promising treatment for NSCLC.
Highlights
It was demonstrated that multifunctional protein APE1 (Apurinic/apyrimidinic endonuclease 1) is closely related to tumor immune microenvironment in a number of investigations, the abundance of tumor infiltrating lymphocytes (TILs) has been shown as a prognosis indicator in some researches
Patients’ characteristics Combined dataset from four Gene Expression Omnibus (GEO) database GSE68465, GSE30219, GSE31210 and GSE50081 comprised of a Correlation between APE1 expression and TILs infiltration To explore the relationship between APE1 expression and TILs infiltration, the abundance of TILs was estimated by using two methods separately, MCPcounter
CD4+ T cells abundance was no more a favorable factor for longer relapse free survival (RFS) in the high APE1 expression groups (P > 0.05; Fig. 2b, d and f). These results suggest that high APE1 expression may cripple the beneficial effects of CD4+ T cells abundance on RFS
Summary
It was demonstrated that multifunctional protein APE1 (Apurinic/apyrimidinic endonuclease 1) is closely related to tumor immune microenvironment in a number of investigations, the abundance of tumor infiltrating lymphocytes (TILs) has been shown as a prognosis indicator in some researches. It remains unclear whether APE1 is involved in the process of TILs affecting the prognosis of patients. A large number of studies indicated that APE1 is related to the first-line chemotherapeutic outcomes in advanced non-small cell lung cancer (NSCLC) [3, 4]. The potential mechanism of APE1 affecting the prognosis of patients has not been fully elucidated
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