NFKBIE is a predictive factor of survival and is correlated with immune infiltration and antigen processing and presentation in hepatocellular carcinoma

Zhang,Yang; Tu,Jinqi; Wang,Jian; Dai,Tiancheng; Zheng,Lin; Sun,Sinan; Tu,Conyin; Li,Heng; Qian,Liting

doi:10.3892/ol.2024.14613

NFKBIE is a predictive factor of survival and is correlated with immune infiltration and antigen processing and presentation in hepatocellular carcinoma

Authors:
- Yang Zhang
- Jinqi Tu
- Jian Wang
- Tiancheng Dai
- Lin Zheng
- Sinan Sun
- Conyin Tu
- Heng Li
- Liting Qian
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Affiliations: Department of Comprehensive Surgery, The First Affiliated Hospital of University of Science and Technology of China West District, Hefei, Anhui 230031, P.R. China, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui 241001, P.R. China, Department of Medical Laboratory Technology, The First Clinical College of Anhui Medical University, Anhui Medical University, Hefei, Anhui 230032, P.R. China, Department of Radiation Oncology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230031, P.R. China
Published online on: August 6, 2024 https://doi.org/10.3892/ol.2024.14613
Article Number: 480
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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