CK2B is a Prognostic Biomarker and a Potential Drug Target for Hepatocellular Carcinoma.

Huiru Dai, Minling Liu, Yuxi Pan, Tingwei Li, Yihang Pan, Zhe-Sheng Chen, Jing Li, Yuchen Liu, Shuo Fang
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Abstract

Background: Although casein kinase II subunit beta (CK2B) was previously reported to be involved in human cancers, such as hepatocellular carcinoma (HCC), there has been no systematic assessment of CK2B in HCC.

Objective: To assess the potential function of CK2B as a prognostic biomarker and possible druggable target in HCC.

Methods: The Cancer Genome Atlas database was accessed to investigate the potential oncogenic and prognostic roles of CK2B in HCC. Diverse analytical methods were used to obtain a fuller understanding of CK2B, including CIBERSORT, The Tumor Immune Estimation Resource (TIMER), gene set enrichment analyses (GSEA), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene ontology (GO). Furthermore, the Comparative Toxicogenomic Database (CTD) was used to identify potential drugs to treat CK2B-overexpressing HCC. Patents for these drugs were reviewed using Patentscope® and Worldwide Espacenet®.

Results: Upregulated CK2B expression was markedly associated with more aggressive pathological features, including G3, G4 (vs. G1, G2), and T2, T3 (vs. T1). Kaplan-Meier survival curves indicated that patients with HCC with higher expression of CK2B had worse overall survival (P = 0.005), progression-free interval (P = 0.001), and disease-specific survival (P = 0.011). GO and KEGG analysis revealed that CK2B dysregulation affects mitotic chromosome condensation, protein stabilization and binding, regulation of signal transduction of p53 class mediator, and cancer-related pathways. GSEA identified six well-known pathways, including MAPK, WNT, Hedgehog, and TGFβ signaling pathways. Finally, CTD identified six compounds that might represent targeted drugs to treat HCC with CK2B overexpression. A review of patents indicated these compounds showed promising anticancer results; however, whether CK2B interacts with these drugs and improves drug outcomes for patients with HCC was not confirmed.

Conclusion: CK2B is a biomarker for HCC prognosis and could be a potential new drug target. Moreover, the association between infiltrating immune cells and CK2B in the HCC tumor microenvironment might provide a solid basis for further investigation and a potent strategy for immunotherapy of HCC.

CK2B是肝细胞癌的预后生物标志物和潜在的药物靶点。
背景:尽管酪蛋白激酶II亚单位β(CK2B)先前被报道与人类癌症如肝细胞癌(HCC)有关,目前尚无对CK2B在HCC中的系统评估。目的:评估CK2B作为HCC预后生物标志物和可能的药物靶点的潜在功能。方法:访问癌症基因组图谱数据库,研究CK2B在肝癌中的潜在致癌和预后作用。使用多种分析方法来更全面地了解CK2B,包括CIBERSORT、肿瘤免疫评估资源(TIMER)、基因集富集分析(GSEA)、京都基因和基因组百科全书(KEGG)和基因本体论(GO)。此外,使用比较毒理学基因组数据库(CTD)来确定治疗CK2B过表达HCC的潜在药物。使用Patentscope®和Worldwide Espacnet®对这些药物的专利进行了审查。结果:CK2B表达上调与更具侵袭性的病理特征显著相关,包括G3、G4(与G1、G2相比)和T2、T3(与T1相比)。Kaplan-Meier生存曲线表明,CK2B表达较高的HCC患者的总生存率(P=0.005)、无进展间期(P=0.001)和疾病特异性生存率(P=0.011)较差。GO和KEGG分析显示,CK2B失调影响有丝分裂染色体凝聚、蛋白质稳定和结合,p53类介导体的信号转导调节以及癌症相关途径。GSEA确定了六种众所周知的途径,包括MAPK、WNT、Hedgehog和TGFβ信号通路。最后,CTD鉴定了六种化合物,它们可能代表治疗CK2B过表达HCC的靶向药物。对专利的审查表明,这些化合物显示出有希望的抗癌效果;然而,CK2B是否与这些药物相互作用并改善HCC患者的药物疗效尚未得到证实。结论:CK2B是HCC预后的生物标志物,可能是一个潜在的新药靶点。此外,HCC肿瘤微环境中浸润性免疫细胞和CK2B之间的相关性可能为进一步研究和HCC免疫治疗提供坚实的基础和有效的策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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