Login Register Cart 0
Generic placeholder image

Recent Patents on Anti-Cancer Drug Discovery

Editor-in-Chief

ISSN (Print): 1574-8928
ISSN (Online): 2212-3970

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

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

Author(s): Huiru Dai, Minling Liu, Yuxi Pan, Tingwei Li, Yihang Pan, Zhe-Sheng Chen, Jing Li*, Yuchen Liu* and Shuo Fang*

Volume 19, Issue 5, 2024

Published on: 27 September, 2023

Page: [622 - 634] Pages: 13

DOI: 10.2174/0115748928262221230925090120

Price: $65

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.

Keywords: Hepatocellular carcinoma, CK2B, oncogene, prognosis, biomarker, drug target, immune cells.

« Previous Next »
[1]
Möller K, Safai Zadeh E, Görg C, et al. Focal liver lesions other than hepatocellular carcinoma in cirrhosis: Diagnostic challenges. J Transl Int Med 2023; 10(4): 308-27.
[http://dx.doi.org/10.2478/jtim-2022-0068] [PMID: 36860624]
[2]
Yang Y, Xiong L, Li M, Jiang P, Wang J, Li C. Advances in radiotherapy and immunity in hepatocellular carcinoma. J Transl Med 2023; 21(1): 526.
[http://dx.doi.org/10.1186/s12967-023-04386-y] [PMID: 37542324]
[3]
Icard P, Simula L, Wu Z, et al. Why may citrate sodium significantly increase the effectiveness of transarterial chemoembolization in hepatocellular carcinoma? Drug Resist Updat 2021; 59: 100790.
[http://dx.doi.org/10.1016/j.drup.2021.100790] [PMID: 34924279]
[4]
Chen L, Wei X, Gu D, Xu Y, Zhou H. Human liver cancer organoids: Biological applications, current challenges, and prospects in hepatoma therapy. Cancer Lett 2023; 555: 216048.
[http://dx.doi.org/10.1016/j.canlet.2022.216048] [PMID: 36603689]
[5]
Cheng AL, Kang YK, Chen Z, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: A phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol 2009; 10(1): 25-34.
[http://dx.doi.org/10.1016/S1470-2045(08)70285-7] [PMID: 19095497]
[6]
Cainap C, Qin S, Huang WT, et al. Linifanib versus Sorafenib in patients with advanced hepatocellular carcinoma: Results of a randomized phase III trial. J Clin Oncol 2015; 33(2): 172-9.
[http://dx.doi.org/10.1200/JCO.2013.54.3298] [PMID: 25488963]
[7]
Strum SW, Gyenis L, Litchfield DW. CSNK2 in cancer: Pathophysiology and translational applications. Br J Cancer 2022; 126(7): 994-1003.
[http://dx.doi.org/10.1038/s41416-021-01616-2] [PMID: 34773100]
[8]
Nickelsen A, Götz C, Lenz F, Niefind K, König S, Jose J. Analyzing the interactome of human CK2β in prostate carcinoma cells reveals HSP70 ‐1 and Rho guanin nucleotide exchange factor 12 as novel interaction partners. FASEB Bioadv 2023; 5(3): 114-30.
[http://dx.doi.org/10.1096/fba.2022-00098] [PMID: 36876296]
[9]
Lin KY, Fang CL, Chen Y, et al. Overexpression of nuclear protein kinase CK2 Beta subunit and prognosis in human gastric carcinoma. Ann Surg Oncol 2010; 17(6): 1695-702.
[http://dx.doi.org/10.1245/s10434-010-0911-9] [PMID: 20087779]
[10]
Zhou F, Xu J, Ding G, Cao L. Overexpressions of CK2β and XIAP are associated with poor prognosis of patients with cholangiocarcinoma. Pathol Oncol Res 2014; 20(1): 73-9.
[http://dx.doi.org/10.1007/s12253-013-9660-y] [PMID: 23828693]
[11]
Brown MS, Diallo OT, Hu M, et al. CK2 modulation of NF-kappaB, TP53, and the malignant phenotype in head and neck cancer by anti-CK2 oligonucleotides in vitro or in vivo via sub-50-nm nanocapsules. Clin Cancer Res 2010; 16(8): 2295-307.
[http://dx.doi.org/10.1158/1078-0432.CCR-09-3200] [PMID: 20371694]
[12]
Yu S, Hu Q, Fan K, Yang C, Gao Y. CSNK2B contributes to colorectal cancer cell proliferation by activating the mTOR signaling. J Cell Commun Signal 2021; 15(3): 383-92.
[http://dx.doi.org/10.1007/s12079-021-00619-1] [PMID: 33928514]
[13]
Team RCR. language and environment for statistical computing: R Foundation for statistical computing. 2020. Available From: https://www.R-project.org/
[14]
Xu X, Yang X, Song Y, et al. Dysregulation of non-coding RNAs mediates cisplatin resistance in hepatocellular carcinoma and therapeutic strategies. Pharmacol Res 2022; 176: 105906.
[http://dx.doi.org/10.1016/j.phrs.2021.105906] [PMID: 34543740]
[15]
Pacciarini MA, Valota O, Kerr D. Use of methoxymorpholino doxorubicin for the treatment of a liver tumor. WO Patent 2000015203, 2000.
[16]
Kong Q, Cong B. Decitabine sustained-release preparation for treating solid tumor. CN Patent 101185629A, 2018.
[17]
Belyakov S, Duvall B, Ferrari D, Hamilton G, Vaal M. Combination of decitabine with cytidine deaminase inhibitor and use thereof in the treatment of cancer. US Patent 2010118010, 2010.
[18]
Faleh A-SFJ. Present invention relates to a treatment for the management of cancer more specially the use of Flutamide antiandrogen drugsa. US patent 20100152298, 2010.
[19]
Alcaraz E, Vilardell J, Borgo C, et al. Effects of CK2β subunit down-regulation on Akt signalling in HK-2 renal cells. PLoS One 2020; 15(1): e0227340.
[http://dx.doi.org/10.1371/journal.pone.0227340] [PMID: 31910234]
[20]
Filhol O, Giacosa S, Wallez Y, Cochet C. Protein kinase CK2 in breast cancer: The CK2β regulatory subunit takes center stage in epithelial plasticity. Cell Mol Life Sci 2015; 72(17): 3305-22.
[http://dx.doi.org/10.1007/s00018-015-1929-8] [PMID: 25990538]
[21]
Nuñez de Villavicencio-Diaz T, Rabalski A, Litchfield D. Protein Kinase CK2: Intricate Relationships within Regulatory Cellular Networks. Pharmaceuticals 2017; 10(4): 27.
[http://dx.doi.org/10.3390/ph10010027] [PMID: 28273877]
[22]
Zhang HX, Jiang SS, Zhang XF, et al. Protein kinase CK2α catalytic subunit is overexpressed and serves as an unfavorable prognostic marker in primary hepatocellular carcinoma. Oncotarget 2015; 6(33): 34800-17.
[http://dx.doi.org/10.18632/oncotarget.5470] [PMID: 26430962]
[23]
Rabjerg M, Guerra B, Oliván-Viguera A, et al. Nuclear localization of the CK2α-subunit correlates with poor prognosis in clear cell renal cell carcinoma. Oncotarget 2017; 8(1): 1613-27.
[http://dx.doi.org/10.18632/oncotarget.13693] [PMID: 27906674]
[24]
Marrero JA, Kulik LM, Sirlin CB, et al. Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the american association for the study of liver diseases. Hepatology 2018; 68(2): 723-50.
[http://dx.doi.org/10.1002/hep.29913] [PMID: 29624699]
[25]
Johnson PJ, Pinato DJ, Kalyuzhnyy A, Toyoda H. Breaking the child-pugh dogma in hepatocellular carcinoma. J Clin Oncol 2022; 40(19): 2078-82.
[http://dx.doi.org/10.1200/JCO.21.02373] [PMID: 35344390]
[26]
Tellapuri S, Sutphin PD, Beg MS, Singal AG, Kalva SP. Staging systems of hepatocellular carcinoma: A review. Indian J Gastroenterol 2018; 37(6): 481-91.
[http://dx.doi.org/10.1007/s12664-018-0915-0] [PMID: 30593649]
[27]
Yau T, Tang VYF, Yao TJ, Fan ST, Lo CM, Poon RTP. Development of hong kong liver cancer staging system with treatment stratification for patients with hepatocellular carcinoma. Gastroenterology 2014; 146(7): 1691-1700.e3.
[http://dx.doi.org/10.1053/j.gastro.2014.02.032] [PMID: 24583061]
[28]
Llovet JM, Bruix J. Prospective validation of the cancer of the liver italian program (CLIP) score: A new prognostic system for patients with cirrhosis and hepatocellular carcinoma. Hepatology 2000; 32(3): 679-80.
[http://dx.doi.org/10.1053/jhep.2000.16475] [PMID: 10991637]
[29]
Yu S, Li L, Cai H, He B, Gao Y, Li Y. Overexpression of NELFE contributes to gastric cancer progression via Wnt/β-catenin signaling-mediated activation of CSNK2B expression. J Exp Clin Cancer Res 2021; 40(1): 54.
[http://dx.doi.org/10.1186/s13046-021-01848-3] [PMID: 33526068]
[30]
Xiao Y, Huang S, Qiu F, et al. Tumor necrosis factor α-induced protein 1 as a novel tumor suppressor through selective downregulation of CSNK2B blocks nuclear factor-κB activation in hepatocellular carcinoma. EBioMedicine 2020; 51: 102603.
[http://dx.doi.org/10.1016/j.ebiom.2019.102603] [PMID: 31901862]
[31]
Calvisi DF. When good transforming growth factor‐β turns bad in hepatocellular carcinoma: Axl takes the stage. Hepatology 2015; 61(3): 759-61.
[http://dx.doi.org/10.1002/hep.27624] [PMID: 25429775]
[32]
Xu Y, Yu X, Sun Z, He Y, Guo W. Roles of lncRNAs Mediating Wnt/β-Catenin Signaling in HCC. Front Oncol 2022; 12: 831366.
[http://dx.doi.org/10.3389/fonc.2022.831366] [PMID: 35356220]
[33]
Ebrahimi N, Kharazmi K, Ghanaatian M, et al. Role of the Wnt and GTPase pathways in breast cancer tumorigenesis and treatment. Cytokine Growth Factor Rev 2022; 67: 11-24.
[http://dx.doi.org/10.1016/j.cytogfr.2022.05.001] [PMID: 35934612]
[34]
Garcia-Lezana T, Lopez-Canovas JL, Villanueva A. Signaling pathways in hepatocellular carcinoma. Adv Cancer Res 2021; 149: 63-101.
[http://dx.doi.org/10.1016/bs.acr.2020.10.002] [PMID: 33579428]
[35]
Yang C, Mai Z, Liu C, Yin S, Cai Y, Xia C. Natural products in preventing tumor drug resistance and related signaling pathways. Molecules 2022; 27(11): 3513.
[http://dx.doi.org/10.3390/molecules27113513] [PMID: 35684449]
[36]
Pollutri D, Gramantieri L, Bolondi L, Fornari F. TP53/MicroRNA interplay in hepatocellular carcinoma. Int J Mol Sci 2016; 17(12): 2029.
[http://dx.doi.org/10.3390/ijms17122029] [PMID: 27918441]
[37]
Shearn CT, Petersen DR. Understanding the tumor suppressor PTEN in chronic alcoholism and hepatocellular carcinoma. Adv Exp Med Biol 2015; 815: 173-84.
[http://dx.doi.org/10.1007/978-3-319-09614-8_10] [PMID: 25427907]
[38]
Tu T, Chen J, Chen L, Stiles BL. Dual-specific protein and lipid phosphatase PTEN and its biological functions. Cold Spring Harb Perspect Med 2020; 10(1): a036301.
[http://dx.doi.org/10.1101/cshperspect.a036301] [PMID: 31548229]
[39]
Angeli D, Salvi S, Tedaldi G. Genetic predisposition to breast and ovarian cancers: How many and which genes to test? Int J Mol Sci 2020; 21(3): 1128.
[http://dx.doi.org/10.3390/ijms21031128] [PMID: 32046255]
[40]
Papa A, Pandolfi PP. The PTEN–PI3K axis in cancer. Biomolecules 2019; 9(4): 153.
[http://dx.doi.org/10.3390/biom9040153] [PMID: 30999672]
[41]
Wang J, Mi S, Ding M, Li X, Yuan S. Metabolism and polarization regulation of macrophages in the tumor microenvironment. Cancer Lett 2022; 543: 215766.
[http://dx.doi.org/10.1016/j.canlet.2022.215766] [PMID: 35690285]
[42]
Wang Z, Wang Y, Gao P, Ding J. Immune checkpoint inhibitor resistance in hepatocellular carcinoma. Cancer Lett 2023; 555: 216038.
[http://dx.doi.org/10.1016/j.canlet.2022.216038] [PMID: 36529238]
[43]
Bai J, Liang P, Li Q, Feng R, Liu J. Cancer immunotherapy - immune checkpoint inhibitors in hepatocellular carcinoma. Recent Patents Anticancer Drug Discov 2021; 16(2): 239-48.
[http://dx.doi.org/10.2174/1574892816666210212145107] [PMID: 33583384]
[44]
Pham L, Kyritsi K, Zhou T, et al. The functional roles of immune cells in primary liver cancer. Am J Pathol 2022; 192(6): 826-36.
[http://dx.doi.org/10.1016/j.ajpath.2022.02.004] [PMID: 35337836]
[45]
Giraldo NA, Becht E, Pagès F, et al. Orchestration and prognostic significance of immune checkpoints in the microenvironment of primary and metastatic renal cell cancer. Clin Cancer Res 2015; 21(13): 3031-40.
[http://dx.doi.org/10.1158/1078-0432.CCR-14-2926] [PMID: 25688160]
[46]
Qi Y, Xia Y, Lin Z, et al. Tumor-infiltrating CD39+CD8+ T cells determine poor prognosis and immune evasion in clear cell renal cell carcinoma patients. Cancer Immunol Immunother 2020; 69(8): 1565-76.
[http://dx.doi.org/10.1007/s00262-020-02563-2] [PMID: 32306075]
[47]
Dai S, Zeng H, Liu Z, et al. Intratumoral CXCL13 + CD8 + T cell infiltration determines poor clinical outcomes and immunoevasive contexture in patients with clear cell renal cell carcinoma. J Immunother Cancer 2021; 9(2): e001823.
[http://dx.doi.org/10.1136/jitc-2020-001823] [PMID: 33589528]

Rights & Permissions Print Cite
Article Metrics
15
1
© 2024 Bentham Science Publishers | Privacy Policy