Dai Huiru, Liu Minling, Pan Yuxi, Li Tingwei, Pan Yihang, Chen Zhe-Sheng, Li Jing, Liu Yuchen, Fang Shuo
Department of Oncology, The Seventh Affiliated Hospital Sun Yat-sen University, Shenzhen, Guangdong, 518107, PR China.
Big Data Centre, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.
Recent Pat Anticancer Drug Discov. 2024;19(5):622-634. doi: 10.2174/0115748928262221230925090120.
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.
To assess the potential function of CK2B as a prognostic biomarker and possible druggable target in HCC.
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 -overexpressing HCC. Patents for these drugs were reviewed using Patentscope and Worldwide Espacenet.
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 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.
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.
尽管先前有报道称酪蛋白激酶IIβ亚基（CK2B）参与人类癌症，如肝细胞癌（HCC），但尚未对HCC中的CK2B进行系统评估。
评估CK2B作为HCC预后生物标志物的潜在功能以及可能的可成药靶点。
访问癌症基因组图谱数据库，研究CK2B在HCC中的潜在致癌和预后作用。使用多种分析方法以更全面地了解CK2B，包括CIBERSORT、肿瘤免疫评估资源（TIMER）、基因集富集分析（GSEA）、京都基因与基因组百科全书（KEGG）和基因本体论（GO）。此外，使用比较毒理基因组学数据库（CTD）来鉴定治疗CK2B过表达HCC的潜在药物。使用Patentscope和世界知识产权局专利数据库检索这些药物的专利。
CK2B表达上调与更具侵袭性的病理特征显著相关，包括G3、G4（vs.G1、G2）以及T2、T3（vs.T1）。Kaplan-Meier生存曲线表明，CK2B表达较高的HCC患者总生存期较差（P = 0.005）、无进展生存期较差（P = 0.001）以及疾病特异性生存期较差（P = 0.011）。GO和KEGG分析表明，CK2B失调影响有丝分裂染色体凝聚、蛋白质稳定和结合、p53类介质信号转导调节以及癌症相关途径。GSEA鉴定出六个著名途径，包括MAPK、WNT、Hedgehog和TGFβ信号通路。最后，CTD鉴定出六种可能代表治疗CK2B过表达HCC的靶向药物的化合物。专利检索表明这些化合物显示出有前景的抗癌结果；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。
CK2B是HCC预后的生物标志物，可能是一个潜在的新药物靶点。此外，HCC肿瘤微环境中浸润免疫细胞与CK2B之间的关联可能为进一步研究提供坚实基础，并为HCC免疫治疗提供有效策略。
