APE1 may influence CD4+ naïve T cells on recurrence free survival in early stage NSCLC

Abstract

Background It 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. Methods Genome-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). Results The 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. Conclusion These 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.

Correlation of SIDT1 with Poor Prognosis and Immune Infiltration in Patients with Non-Small Cell Lung Cancer

“… 25 Dendritic cells play an essential role in activating anti-tumor T lymphocytes to express specific antigens. 26 The impaired function of tumor infiltration may severely affect the body’s anti-tumor immune response, further affecting the development and progression of NSCLC and consequently the survival of patients. 27 Therefore, NCAPG affects the prognosis of NSCLC by influencing the immune status of patients.…”

Molecular Characterization, Tumor Microenvironment Association, and Drug Susceptibility of DNA Methylation-Driven Genes in Renal Cell Carcinoma

“…We further explored the relationship between tumor-infiltrating immune cells and the risk score with seven common acceptable methods of estimating the infiltrating immune cells, including TIMER (Bu F, 2021), CIBERSORT ( Bu et al, 2021 ), xCell ( Oshi et al, 2021 ), quanTIseq ( Finotello et al, 2019 ), MCPcounter ( Li et al, 2021 ), EPIC ( Zeng et al, 2021 ), and CIBERSORT-ABS ( Tamminga et al, 2020 ). The synthetical analysis showed that the risk score was more positively related to tumor-infiltrating immune cells.…”

Molecular Characterization, Clinical Significance, Tumor Microenvironment Association and Drug Susceptibility of DNA Methylation-Driven Genes in Renal Cell Carcinoma

“…CIBERSORT [49], XCELL [50], QUANTISEQ [51], MCPcounter [52], EPIC [53], and CIBERSORT-ABS [54]. The synthetical analysis showed that risk score was more positively related to tumor-in ltrating immune cells.…”