NFKBIE Is a Predictive Factor of Survival and Is Correlated With Immune Infiltration, Antigen Processing, And Presentation In Hepatocellular Carcinoma

Author:

Qian Liting1,Li Heng2,Tu Jinqi3,Zhang Yang2,Dai Tiancheng4,Sun Sinan1,Wang Jian2,Tu Congyin2,Zheng Lin2

Affiliation:

1. The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230031 China

2. Department of Comprehensive Surgery, The First Affiliated Hospital of University of Science and Technology of China (USTC) West District

3. The First Affiliated Hospital of Wannan Medical College(Yijishan Hospital of Wannan Medical College), Wuhu, China

4. Anhui Medical University

Abstract

Abstract Background The important role of the NFκBpathway in tumor development has long been recognized. but the role of the NFκB inhibitor family in liver cancer has not been studied. Hepatocellular carcinoma(HCC)has become a serious public health burden with high incidence, poor prognosis, and early detection, especially in Asia where hepatitis is prevalent. Methods The transcript level of the NFκB inhibitor family was investigated in HCC and normal tissues using Metabolic Gene Rapid Visualizer, UALCAN, and Tumor Immune Estimation Resource database(TIMER)respectively. Survival curves of NFKBIE were obtained using the Kaplan-Meier database. Genes co-expressed with NFKBIE in hepatocellular carcinoma were studied by LinkedOmics and Hepatocellular Carcinoma Database(HCCDB) respectively. Protein-protein interaction (PPI) Networks, gene ontology, and KEGG enrichment pathway analyses provide a novel method for investigating the NFKBIE mechanism in HCC. Using the TIMER database, the connection between immune infiltration and NFKBIE was determined. RNA-Seq was used to evaluate NFKBIE's function in HCC and its impact on proliferation and migration. Western Blot was used to confirm the expression of NFKBIE in HCC cell lines.In addition, we demonstrated NFKBIE overexpression in HCC using tissue microarrays encompassing 80 pairs of HCC and normal liver tissues. Results: NFKBIE was the only NFκBinhibitor in its family with high expression and a better prognosis in HCC.NFKBIE was correlated with clinical characteristics such as tumor grade, TP53 mutation status, and tumor stage.GSCA database suggested that NFKBIE might inhibit the PI3K/AKT, RAS/MAPK, RTK, and TSC/mTOR pathways. In addition, NFKBIE was significantly associated with B cell immune infiltration, and our RNA-Seq data showed that NFKBIE knockout significantly affected antigen presentation and hepatocellular carcinoma pathways. Immunohistochemistry on microarrays of tissue samples revealed that NFKBIE was overexpressed in various stages of HCC. Inhibition of NFKBIE also decreased the growth and migration of hepatocellular carcinoma cells. Conclusion: Due to its prognostic value and overexpression in hepatocellular carcinoma, NFKBIE distinguished itself from other NFκB inhibitors. As such, it may provide a novel prognostic indicator and immunotherapeutic target in HCC.

Publisher

Research Square Platform LLC

Reference29 articles.

1. Chemoembolization for intermediate HCC: is there proof of survival benefit?;Forner A;J HEPATOL,2012

2. Gemcitabine plus oxaliplatin (GEMOX) in patients with advanced hepatocellular carcinoma (HCC);Louafi S;CANCER-AM CANCER SOC,2007

3. Dominant-negative NFKBIA mutation promotes IL-1β production causing hepatic disease with severe immunodeficiency;Tan EEK;J CLIN INVEST,2020

4. Hayden MS, Ghosh S. Shared Principles in NF-κB Signaling. CELL (2008) 132: 344–362.

5. Determining consistent prognostic biomarkers of overall survival and vascular invasion in hepatocellular carcinoma;Menyhart ONAGB;R Soc Open Sci,2018

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3