Abstract
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the deadliest diseases affecting humans. Its incidence has been increasing over the last decade. It is characterized by poor prognosis as well as lack of therapeutic regimens for patients in the advanced stages. It is therefore important to develop effective biomarkers for diagnosis, prognosis, and immunotherapy of HCC. Research suggests that the NF-κB family plays vital roles in immune response, inflammation, tumorigenesis, and the progress of malignancy in various cancers. However, its role in HCC remains unidentified. Methodology. The expression and clinical significance of the NF-κB family in HCC were analyzed using several bioinformatics tools including UALCAN, The Human Protein Atlas, GEPIA, GSCALite, David, GeneMANIA, and TIMER. RESULTS: The mRNA expression levels of RelA, RelB, NF-κB1, and NF-κB2 were significantly elevated in HCC. The mRNA levels of RelB and NF-κB2 were significantly upregulated in HCC tissues compared to normal liver tissues in subgroup analyses based on patient's race, gender, age, weight, tumor grade, cancer stage, and nodal metastasis status. Moreover, HCC patients with elevated levels of RelB and NF-κB2 had a worse overall survival and disease-free survival. Methylation downregulated the expressions of RelA, RelB, and NF-κB1 in HCC. NF-κB family was also significantly involved in various hallmark cancer-related pathways such as the apoptosis, EMT, RTK, and cell cycle pathways. Similarly, the expression of RelB and NF-κB2 was positively correlated with the abundance of immune cells and the expression of immune biomarkers. Several kinase and miRNA targets of RelB and NF-κB2 were also identified. CONCLUSION: RelB and NF-κB2 are potential biomarkers for the diagnosis, prognosis, and immunotherapy of HCC.