NIFK, an independent prognostic biomarker of hepatocellular carcinoma, is correlated with immune infiltration
Abstract
Background: The molecular mechanisms that lead to hepatocellular carcinoma (HCC), a highly common malignant tumor, are currently unclear. In fact, while the nucleolar protein that interacts with the FHA domain of pKi-67 (NIFK) is known to promote lung cancer progression, its specific role in HCC remains unknown.
Results: In HCC tissues, NIFK was significantly overexpressed in comparison with normal tissues. In The Cancer Genome Atlas (TCGA) database, NIFK expression showed a good prediction value according to an ROC curve and it was linked to poor progression-free interval, disease-specific survival and overall survival. Furthermore, the level of NIFK expression in HCC was significantly correlated with tumor stage, AFP (ng/mL), OS event, DSS event and PFI event. Based on GSEA evaluations, differentially expressed NIFK genes exhibited enrichment for fatty acid metabolism, oxidative phosphorylation as well as cancer, cell cycle, MAPK, TGF, WNT and NOTCH signaling pathways. The TIMER database analysis further revealed positive associations between NIFK expression and the immune cells, such as dendritic cells, neutrophils, macrophages, CD4+ T cells, CD8+ T cells and B cells. Also, the NIFK expression was positively correlated with immune checkpoints (PD1/PD-L1 and CTLA4). The experimental verification determined that NIFK knockdown could thwart HCC cellular properties of proliferation, metastasis and invasiveness. Univariate and multivariate Cox hazard regression validated NIFK expression as an independent prognostic marker in HCC.
Conclusions: NIFK has theragnostic potential as a separate prognostic factor or novel biomarker involved in the immune infiltration of HCC.