Increased NFE2L3 Is Associated With A Poor Prognosis And Immune Infiltration In Hepatocellular Carcinoma

ObjectiveHepatocellular carcinoma is one of the most common cancers worldwide,with high morbidity and mortality.NFE2L3 has been identified as having a potential role in tumorigenesis.This study mainly explored the role of NFE2L3 in the prognosis of hepatocellular carcinoma and its regulatory mechanism on the immune microenvironment.MethodsThis study mainly used the liver cancer data set(n _tumor=371;n _normal=50)of the TCGA database to analyze the expression and prognostic value of NFE2L3 and used liver cancer cell lines for Western blotting in vitro validation.The biological functions and pathways of NFE2L3 and its co-expressed genes were analyzed by GO and KEGG,and the correlation between NFE2L3 expression and immune infiltration was calculated using x Cell,CIBERSORT,EPIC,MCPCOUNTER,QUANTISEQ and TIMER algorithms.And survival analysis was performed for subgroups of patients by Kaplan-Meier Plotter.ResultsThe expression of NFE2L3 was increased in hepatocellular carcinoma tissues compared with normal tissues（p<0.001）and correlated with tumor stage,grade,and metastatic status.Up-regulation of NFE2L3 expression was predictive of poorer survival in HCC patients（HR,1.20;95%CI,1.04-1.38;p=0.012）.NFE2L3 is involved in various immune-related pathways in hepatocellular carcinoma,such as the proliferation,activation,differentiation,cytokine production,and regulation of various immune cells.Moreover,the expression of NFE2L3 was closely related to the stromal score,immune score,and microenvironment score;the expression of NFE2L3 was related to the infiltration of 26 types of immune cells,including CD4+T cells,macrophages,and dendritic cells.In addition,the expression of NFE2L3 and the degree of immune cell infiltration have different effects on the survival of patients with hepatocellular carcinoma,further suggesting that NFE2L3 may affect the prognosis of patients by regulating the immune microenvironment.This study indicates that NFE2L3 is regulated by upstream transcription factors such as ATF1,CREB1,and CTCF and regulates the expression of downstream genes TP53 and MACF1,which regulate tumor progression.ConclusionHigh expression of NFE2L3 is associated with poor prognosis in patients with hepatocellular carcinoma and affects tumor development by regulating immune cell infiltration in the tumor microenvironment.