Prognostic biomarker NEIL3 and its association with immune infiltration in renal clear cell carcinoma.

BACKGROUND: Kidney renal clear cell carcinoma (KIRC) is a malignant tumor with a high degree of immune infiltration. Identifying immune biomarkers is essential for the treatment of KIRC. Studies have identified the potential of NEIL3 to modulate the immune microenvironment and promote tumor progression. However, the role of NEIL3 in KIRC remains uncertain. This study was to investigate the effect of NEIL3 on the prognosis and immune infiltration of patients with KIRC.

METHODS: TCGA and GEO databases were used to study the expression of NEIL3 in KIRC. Cox regression analysis was used to examine the relationship between the expression of NEIL3 and clinicopathological variables and survival. Furthermore, Gene Set Cancer Analysis (GSCA) was applied to study the impact of NEIL3 methylation on outcomes of KIRC. Through gene ontology (GO) and Gene set enrichment (GSEA) analysis, the biological processes and signal pathways related to NEIL3 expression were identified. In addition, immune infiltration analysis was conducted via CIBERSORT analysis, ssGSEA analysis and TISIDB database.

RESULTS: NEIL3 was overexpressed in KIRC, and it was significantly related with histologic grade, pathologic stage, T stage, M stage, and vital status of KIRC patients ( P < 0.001). The expression of NEIL3 was associated with worse outcomes. Univariate and multivariate Cox analysis showed that NEIL3 may be an indicator of adverse outcomes in KIRC. GSEA analysis revealed that NEIL3 may be involved in signal pathways including cell cycle, DNA replication, mismatch repair, P53 signal pathway, and antigen processing and presentation. In addition, immune infiltration analysis showed a positive correlation between NEIL3 expression and multiple immune cells (activated CD8 T cells, activated dendritic cells, myeloid-derived suppressor cells, follicular helper T cells, and regulatory T cells) and immunoinhibitors (PD1, CTLA4, LAG3, TIGHT, IL10, and CD96).

CONCLUSION: NEIL3 is a potential independent biomarker of KIRC, which is relevant to immune infiltration.