RESUMO
The important role of the nuclear factor κB (NFκB) pathway in tumour development has long been recognized; however, the role of the NFκB inhibitor family in liver cancer has not been elucidated. Hepatocellular carcinoma (HCC) is a serious public health burden with a high incidence, poor prognosis, and early detection, especially in Asia, where hepatitis is prevalent. In the present study, the mRNA expression level of the NFκB inhibitor family was assessed in HCC and normal tissues using the Metabolic Gene Rapid Visualizer, University of Alabama at Birmingham Cancer Data Analysis Portal, and the Tumor Immune Estimation Resource database (TIMER). Survival curves of nuclear factor of κ light polypeptide gene enhancer in B-cells inhibitor (NFKBI)E were obtained using the Kaplan-Meier method. Genes co-expressed with NFKBIE in HCC samples were studied using data from the LinkedOmics and the Hepatocellular Carcinoma Databases. Protein-protein interaction networks, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment pathway analyses were used to assess the NFKBIE mechanism in HCC. Using the TIMER database, the association between immune infiltration and NFKBIE was determined. RNA-sequencing (RNA-seq) was used to evaluate the function of NFKBIE in HCC and its impact on proliferation and migration. Western blotting was used to confirm the expression of NFKBIE in HCC cell lines. In addition, NFKBIE overexpression in HCC was demonstrated using tissue microarrays encompassing 80 pairs of HCC and normal liver tissues. NFKBIE was the only NFκB inhibitor with high expression and an improved prognosis in HCC compared with other NFκB inhibitors. NFKBIE was correlated with clinical characteristics, such as tumour grade, tumour protein P53 mutation status and tumour stage. Data obtained from Gene Set Cancer Analysis suggested that NFKBIE may inhibit the PI3K/AKT, RAS/MAPK, RTK and TSC/mTOR pathways. In addition, NFKBIE was significantly associated with B-cell immune infiltration and the RNA-seq data demonstrated that knockdown of NFKBIE significantly affected 'Antigen processing and presentation' and 'hepatocellular carcinoma' pathways. Immunohistochemistry of microarrays of tissue samples revealed that NFKBIE was overexpressed in several stages of HCC. Finally, inhibition of NFKBIE decreased the proliferation and migration of HCC cells. In conclusion, due to its prognostic value and overexpression in HCC, NFKBIE distinguished itself from other NFκB inhibitors. As such, it may provide a novel prognostic indicator and immunotherapeutic target for HCC.