NCF1/2/4 Are Prognostic Biomarkers Related to the Immune Infiltration of Kidney Renal Clear Cell Carcinoma

Abstract

Neutrophil cytoplasmic factor 1/2/4 (NCF1/2/4) belongs to the NADPH oxidase complex, which is a cytoplasmic component, and its polymorphism is the main factor related to autoimmune diseases, which is probably caused by the regulation of peroxide. They also play a role in tumor growth and metastasis. This research is aimed at evaluating the biological function and prognostic role of NCF1, NCF2, and NCF4 genes in kidney renal clear cell carcinoma (KIRC) by using multiple online bioinformatics website, including Oncomine, GEPIA, UALCAN, Kaplan–Meier Plotter, TIMER, TISIDB, cBioPortal, LinkedOmics, GeneMANIA, and DAVID databases. The mRNA levels of NCFs were higher in KIRC tissues than in normal tissues. The overexpression of NCFs was significantly correlated with advanced pathological grades and individual cancer stages in KIRC. Meanwhile, the expressions of NCFs played an important role in the tumorigenesis and progression of KIRC. Prognostic value analysis suggested that high transcription levels of NCF1/4 were associated with poor overall survival in KIRC patients. In addition, results from the LinkedOmics database showed that the KEGG pathway related to NCFs mainly focused on immune activation and immune regulation function. NCF genetic alterations, including copy number amplification, missense mutation, and deep deletion, could be found through the cBioPortal database. Further, NCF expression was significantly correlated with infiltration levels of various immune cells as well as immune signatures. Protein-protein interaction network and enrichment analysis of NCF1/2/4 in KIRC showed that NCF coexpressed genes mainly associated with diverse immune marker sets showed significance. Overall, these results indicated that NCFs could be prognostic biomarkers as well as effective targets for diagnosis in KIRC.