中文｜English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 40 Issue 7
Jul.  2024
Turn off MathJax
Article Contents
Article Navigation >  Journal of Clinical Hepatology  > 2024  >  40(7): 1390-1396

Expression and clinical significance of cell cycle protein-dependent kinase 1 and aurora kinase A in the serum of patients with hepatitis B virus-related hepatocellular carcinoma

DOI: 10.12449/JCH240717
  • 1.

    The First Clinical Medical College of Gansu University of Chinese Medicine，Lanzhou 730000，China

  • 2.

    Department of Gastroenterology，Gansu Provincial Hospital，Lanzhou 730000，China

Research funding:

National Natural Science Foundation of China (818615010);

Gansu Provincial Outstanding Graduate Student “Star of Innovation” Project (2023CXZX-754)

More Information
  • Corresponding author: MA Yanhua， 617747928@ qq.com （ORCID： 0009-0000-2240-6413）
  • Received Date: 2023-10-17
  • Accepted Date: 2024-01-16
  • Published Date: 2024-07-25
    Abstract
  •   Objective  To investigate the value of serum cell cycle protein-dependent kinase 1 （CDK1） and aurora kinase A （AURKA） in the diagnosis of patients with hepatitis B virus-related hepatocellular carcinoma （HBV-HCC）.  Methods  A total of 50 HBV-HCC patients， 50 patients with hepatitis B virus-related liver cirrhosis （HBV-LC）， and 50 chronic hepatitis B （CHB） patients who were hospitalized in Department of Gastroenterology， Gansu Provincial Hospital， from June 2022 to December 2023 were enrolled， and 50 healthy individuals， matched for age and sex， who received physical examination at Physical Examination Center during the same period of time were enrolled as control group. Related data were recorded for all patients， including age， sex， complications， and the results of routine blood test， liver function， and coagulation for the first time after admission. ELISA was used to measure the serum levels of CDK1 and AURKA. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups； the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups and the least significant difference Bonferroni test was used for further comparison between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. The Spearman correlation analysis was used to investigate the correlation between CDK1 and AURKA， and the receiver operating characteristic （ROC） curve and the area under the ROC curve （AUC） were used to investigate the value of CDK1 and AURKA in the diagnosis of HBV-HCC.  Results  There were significant differences in liver function parameters between the HBV-HCC patients and the control group （all P<0.05）； there were significant differences between the CHB group and the HBV-HCC group in albumin， Glb， direct bilirubin， aspartate aminotransferase （AST）， gamma-glutamyl transpeptidase （GGT）， and alkaline phosphatase （all P<0.05）； there were significant differences between the HBV-LC group and the HBV-HCC group in Glb， AST， and GGT （all P<0.05）. The HBV-HCC group had significantly higher serum levels of CDK1 and AURKA than the HBV-LC group， the CHB group， and the control group （all P<0.05）. There was a significant positive correlation between CDK1 and AURKA in the overall study population and the HBV-HCC patients （r=0.526 6 and 0.815 2， P<0.001）. With the control group as reference， CDK1 had an AUC of 0.832 3 in the diagnosis of HBV-HCC， with a sensitivity of 92.86% and a specificity of 75%， and AURKA had an AUC of 0.886 6 in the diagnosis of HCC， with a sensitivity of 95.80% and a specificity of 74%. With the CHB group as reference， CDK1 had an AUC of 0.833 3 in the diagnosis of HBV-HCC， with a sensitivity of 93.75% and a specificity of 75%， and AURKA had an AUC of 0.972 7 in the diagnosis of HBV-HCC， with a sensitivity of 95.83% and a specificity of 91.67%. With the HBV-LC group as reference， CDK1 had an AUC of 0.608 5 in the diagnosis of HBV-HCC， with a sensitivity of 66.67% and a specificity of 54.17%， and AURKA had an AUC of 0.762 2 in the diagnosis of HBV-HCC， with a sensitivity of 95.83% and a specificity of 47.92%.  Conclusion  The serum levels of CDK1 and AURKA increase with the progression of hepatitis B-associated chronic liver disease， and significant increases in serum CDK1 and AURKA have a certain value in the diagnosis of HBV-HCC.

     

    • FullText(HTML)
  • loading
    • References(33)
  • [1]
    BRAY F, FERLAY J, SOERJOMATARAM I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018, 68( 6): 394- 424. DOI: 10.3322/caac.21492.
    [2]
    CHEDID MF, KRUEL CRP, PINTO MA, et al. Hepatocellular carcinoma: Diagnosis and operative management[J]. Arq Bras Cir Dig, 2017, 30( 4): 272- 278. DOI: 10.1590/0102-6720201700040011.
    [3]
    CHEN DH, HONG M, ZHANG YL, et al. Expression and clinical significance of HBx and miR-122 in hepatitis B related hepatocellular carcinoma[J]. J Mol Diagn Ther, 2023, 15( 2): 240- 243, 248. DOI: 10.19930/j.cnki.jmdt.2023.02.029.

    陈东海, 洪玫, 张依琳, 等. 乙肝相关性肝细胞癌中HBx、miR-122表达及临床意义[J]. 分子诊断与治疗杂志, 2023, 15( 2): 240- 243, 248. DOI: 10.19930/j.cnki.jmdt.2023.02.029.
    [4]
    ZHU HZ, ZHOU WJ, WAN YF, et al. Downregulation of orosomucoid 2 acts as a prognostic factor associated with cancer-promoting pathways in liver cancer[J]. World J Gastroenterol, 2020, 26( 8): 804- 817. DOI: 10.3748/wjg.v26.i8.804.
    [5]
    HUANG YH, SRAMKOSKI RM, JACOBBERGER JW. The kinetics of G2 and M transitions regulated by B cyclins[J]. PLoS One, 2013, 8( 12): e80861. DOI: 10.1371/journal.pone.0080861.
    [6]
    ZOU YP, RUAN SY, JIN L, et al. CDK1, CCNB1, and CCNB2 are prognostic biomarkers and correlated with immune infiltration in hepatocellular carcinoma[J]. Med Sci Monit, 2020, 26: e925289. DOI: 10.12659/MSM.925289.
    [7]
    HANAHAN D, WEINBERG RA. Hallmarks of cancer: The next generation[J]. Cell, 2011, 144( 5): 646- 674. DOI: 10.1016/j.cell.2011.02.013.
    [8]
    JENG YM, PENG SY, LIN CY, et al. Overexpression and amplification of Aurora-A in hepatocellular carcinoma[J]. Clin Cancer Res, 2004, 10( 6): 2065- 2071. DOI: 10.1158/1078-0432.ccr-1057-03.
    [9]
    Bureau of Medical Administration, National Health Commission of the People’s Republic of China. Guidelines for diagnosis and treatment of primary liver cancer in China(2019 edition)[J]. J Clin Hepatol, 2020, 36( 2): 277- 292. DOI: 10.3969/j.issn.1001-5256.2020.02.007.

    中华人民共和国国家卫生健康委员会医政医管局. 原发性肝癌诊疗规范(2019年版)[J]. 临床肝胆病杂志, 2020, 36( 2): 277- 292. DOI: 10.3969/j.issn.1001-5256.2020.02.007.
    [10]
    Chinese Society of Hepatology, Chinese Medical Association. Chinese guidelines on the management of liver cirrhosis[J]. J Clin Hepatol, 2019, 35( 11): 2408- 2425. DOI: 10.3969/j.issn.1001-5256.2019.11.006.

    中华医学会肝病学分会. 肝硬化诊治指南[J]. 临床肝胆病杂志, 2019, 35( 11): 2408- 2425. DOI: 10.3969/j.issn.1001-5256.2019.11.006.
    [11]
    Chinese Society of Hepatology, Chinese Medical Association; Chinese Society of Infectious Diseases, Chinese Medical Association. Guidelines for the prevention and treatment of chronic hepatitis B(version 2022)[J]. Infect Dis Inf, 2023, 36( 1): 1- 17. DOI: 10.3969/j.issn.1007-8134.2023.01.01..

    中华医学会肝病学分会, 中华医学会感染病学分会. 慢性乙型肝炎防治指南(2022年版)[J]. 传染病信息, 2023, 36( 1): 1- 17. DOI: 10.3969/j.issn.1007-8134.2023.01.01.
    [12]
    LI J, HAN X, YU XN, et al. Clinical applications of liquid biopsy as prognostic and predictive biomarkers in hepatocellular carcinoma: Circulating tumor cells and circulating tumor DNA[J]. J Exp Clin Cancer Res, 2018, 37( 1): 213. DOI: 10.1186/s13046-018-0893-1.
    [13]
    MA CY, FU YL, ZHANG ZL, et al. The value of contrast-enhanced ultrasound in evaluating the efficacy of microwave ablation for hepatocellular carcinoma and predicting local recurrence[J]. Clin J Med Offic, 2023, 51( 8): 850- 853. DOI: 10.16680/j.1671-3826.2023.08.21.

    马春燕, 符叶柳, 张植兰, 等. 超声造影对肝细胞癌微波消融疗效评估及对局部复发预测价值研究[J]. 临床军医杂志, 2023, 51( 8): 850- 853. DOI: 10.16680/j.1671-3826.2023.08.21.
    [14]
    MALOV SI, MALOV IV, DVORNICHENKO VV, et al. Application of alpha-fetoprotein and osteopontin combination for early diagnosis of hepatocellular carcinoma associated with hepatitis C[J]. Klin Lab Diagn, 2019, 64( 10): 607- 612. DOI: 10.18821/0869-2084-2019-64-10-607-612.
    [15]
    YU XP, YANG RY, HE ZM, et al. Establishment and validation of nomogram of cancer specific survival of patients with hepatocellular carcinoma with negative alpha fetoprotein based on SEER Database[J]. J Jilin Univ(Med Edit), 2024, 50( 1): 188- 197. DOI: 10.13481/j.1671-587X.20240123.

    余孝鹏, 杨仁义, 贺佐梅, 等. 基于SEER数据库建立和验证甲胎蛋白阴性肝细胞癌患者癌症特异生存期的列线图[J]. 吉林大学学报(医学版), 2024, 50( 1): 188- 197. DOI: 10.13481/j.1671-587X.20240123.
    [16]
    PENG QZ, HAO JW, QIN Y, et al. Effect of DNA damage repair pathway mediated by AURKA on HepG2 of liver cancer cells[J]. Chongqing Med, 2021, 50( 1): 1- 7. DOI: 10.3969/j.issn.1671-8348.2021.01.001.

    彭期臻, 郝剑文, 秦宇, 等. AURKA介导DNA损伤修复通路对肝癌细胞HepG2的影响[J]. 重庆医学, 2021, 50( 1): 1- 7. DOI: 10.3969/j.issn.1671-8348.2021.01.001.
    [17]
    ZHANG L, HUANG Y, LING JJ, et al. Screening and function analysis of hub genes and pathways in hepatocellular carcinoma via bioinformatics approaches[J]. Cancer Biomark, 2018, 22( 3): 511- 521. DOI: 10.3233/CBM-171160.
    [18]
    BAO ZY, LU L, LIU XY, et al. Association between the functional polymorphism Ile31Phe in the AURKA gene and susceptibility of hepatocellular carcinoma in chronic hepatitis B virus carriers[J]. Oncotarget, 2017, 8( 33): 54904- 54912. DOI: 10.18632/oncotarget.18613.
    [19]
    LIU C, ZHU XX, JIA YQ, et al. Dasatinib inhibits proliferation of liver cancer cells, but activation of Akt/mTOR compromises dasatinib as a cancer drug[J]. Acta Biochim Biophys Sin, 2021, 53( 7): 823- 836. DOI: 10.1093/abbs/gmab061.
    [20]
    LI XC, XU WQ, KANG W, et al. Genomic analysis of liver cancer unveils novel driver genes and distinct prognostic features[J]. Theranostics, 2018, 8( 6): 1740- 1751. DOI: 10.7150/thno.22010.
    [21]
    WANG LL, JIN XH, CAI MY, et al. AGBL2 promotes cancer cell growth through IRGM-regulated autophagy and enhanced Aurora A activity in hepatocellular carcinoma[J]. Cancer Lett, 2018, 414: 71- 80. DOI: 10.1016/j.canlet.2017.11.003.
    [22]
    CHEN CL, SONG GY, XIANG J, et al. AURKA promotes cancer metastasis by regulating epithelial-mesenchymal transition and cancer stem cell properties in hepatocellular carcinoma[J]. Biochem Biophys Res Commun, 2017, 486( 2): 514- 520. DOI: 10.1016/j.bbrc.2017.03.075.
    [23]
    GOOS JACM, COUPE VMH, DIOSDADO B, et al. Aurora kinase A(AURKA) expression in colorectal cancer liver metastasis is associated with poor prognosis[J]. Br J Cancer, 2013, 109( 9): 2445- 2452. DOI: 10.1038/bjc.2013.608.
    [24]
    TANG AQ, GAO KY, CHU LL, et al. Aurora kinases: Novel therapy targets in cancers[J]. Oncotarget, 2017, 8( 14): 23937- 23954. DOI: 10.18632/oncotarget.14893.
    [25]
    ZHANG LJ, SHI H, JIANG ZY, et al. The mechanism of AURKA regulation of tumor cisplatin resistance[J]. Chem Life, 2023, 43( 8): 1268- 1276. DOI: 10.13488/j.smhx.20220609.

    张丽君, 石皓, 姜卓言, 等. AURKA调控肿瘤顺铂耐药机制[J]. 生命的化学, 2023, 43( 8): 1268- 1276. DOI: 10.13488/j.smhx.20220609.
    [26]
    WU CX, WANG XQ, CHOK SH, et al. Blocking CDK1/PDK1/β-Catenin signaling by CDK1 inhibitor RO3306 increased the efficacy of sorafenib treatment bytargeting cancer stem cells in a preclinical model of hepatocellular carcinoma[J]. Theranostics, 2018, 8( 14): 3737- 3750. DOI: 10.7150/thno.25487.
    [27]
    TANG WW, CHEN ZY, ZHANG WL, et al. The mechanisms of sorafenib resistance in hepatocellular carcinoma: Theoretical basis and therapeutic aspects[J]. Signal Transduct Target Ther, 2020, 5( 1): 87. DOI: 10.1038/s41392-020-0187-x.
    [28]
    YAN M, BAI RX, CHENG S, et al. Expression and significance of cyclin-dependent kinase 1 in human colorectal cancer[J]. Chin J Clin Dr, 2021, 49( 9): 1080- 1082. DOI: 10.3969/j.issn.2095-8552.2021.09.021.

    闫鸣, 白日星, 程石, 等. 细胞周期蛋白依赖性激酶1在人结直肠癌组织中的表达意义[J]. 中国临床医生杂志, 2021, 49( 9): 1080- 1082. DOI: 10.3969/j.issn.2095-8552.2021.09.021.
    [29]
    FANG XT, WU YY, YU TT, et al. Fusobacterium nucleatum promotes colorectal cancer by up-regulating Cdk1 through intestinal metabolite sodium butyrate[J]. Chin J Cell Biol, 2021, 43( 5): 979- 990. DOI: 10.11844/cjcb.2021.05.0009.

    方晓婷, 吴依依, 余婷婷, 等. 具核梭杆菌通过调节肠道代谢产物丁酸钠上调Cdk1促进结直肠癌发展[J]. 中国细胞生物学学报, 2021, 43( 5): 979- 990. DOI: 10.11844/cjcb.2021.05.0009.
    [30]
    NOZOE T, TAKAHASHI I, BABA H, et al. Relationship between intracellular localization of p34cdc2 protein and differentiation of esophageal squamous cell carcinoma[J]. J Cancer Res Clin Oncol, 2005, 131( 3): 179- 183. DOI: 10.1007/s00432-004-0607-2.
    [31]
    MA XL, HUANG SH, HUANG JA, et al. Expression and significance of CyclinB1 and CDK1 in gastric cancer[J]. Chin J Curr Adv Gen Surg, 2004, 7( 5): 272- 274. DOI: 10.3969/j.issn.1009-9905.2004.05.007.

    马晓丽, 黄淑红, 黄敬爱, 等. CyclinB1、CDK1在胃癌中的表达及其意义[J]. 中国现代普通外科进展, 2004, 7( 5): 272- 274. DOI: 10.3969/j.issn.1009-9905.2004.05.007.
    [32]
    SU Y, PAN SJ, LI ZQ, et al. Multiplex imaging and cellular target identification of kinase inhibitors via an affinity-based proteome profiling approach[J]. Sci Rep, 2015, 5: 7724. DOI: 10.1038/srep07724.
    [33]
    MALUMBRES M, BARBACID M. Cell cycle, CDKs and cancer: A changing paradigm[J]. Nat Rev Cancer, 2009, 9( 3): 153- 166. DOI: 10.1038/nrc2602.
    • Relative Articles
    • Supplements(0)
    • Cited By
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(3)  / Tables(3)

    Get Citation
    PDF
    XML

    Article Metrics

    Article views (380) PDF downloads(26) Cited by()
    Proportional views
    Related
        

    The first journal specializing in hepatobiliary and pancreatic diseases in China

    Supervisor：Ministry of Education of the People's Republic of China

    Sponsor：Jilin University

    Academic Support: Chinese Society of Hepatology，Chinese Medical Association

    Address: 461 Xinjiang Road, Changchun

    Submit：0431-88782044

    Peer review：0431-88783542

    Email：lcgdb@vip.163.com

    About Journal

    Submission Guideline

    Journal Online

    Hepatobiliary College

    Guidelines

    YesterdayIP[]YesterdayPV[]TodayIP[]TodayPV[]Online[]

    Website Design © 2020 Editorial Board of Journal of Clinical Hepatology 吉ICP备10000617号-1 Supported by: Beijing Renhe Information Technology Co. Ltd  

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return