中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 35 Issue 3
Mar.  2019
Turn off MathJax
Article Contents

Expression and clinical significance of protein kinase CK2β in hepatocellular carcinoma

DOI: 10.3969/j.issn.1001-5256.2019.03.019
Research funding:

 

  • Received Date: 2018-10-24
  • Published Date: 2019-03-20
  • Objective To investigate the expression and clinical significance of protein kinase CK2β in hepatocellular carcinoma ( HCC) tissue and the association of CK2β expression with patient prognosis. Methods HCC tissue and adjacent tissue samples were collected from127 HCC patients Who were diagnosed in Department of Hepatopancreatobiliary Surgery, The first Affiliated Hospital of Zhengzhou Universi-ty from Januany 2012 to June 2013, and immunohistochemistry was used to measure the expression of CK2β. The association of CK2β ex-pression with clinical features of HCC patients was analyzed. A total of 20 HCC tissue samples, 20 adjacent tissue samples, 20 cirrhotic tis-sue samples, and 20 normal liver tissue samples were collected from March to June 2018 in our hospital, and Western blot and real-timePCR were used to measure the protein and mRNA expression of CK2β in these tissue samples. A one-way analysis of variance was used forcomparison of means between multiple groups, and Bonferroni test was used for further comparison between two groups; the chi-square testwas used for comparison of categorical data between groups. The Mann-Whitney U test or the Kruskal-Wallis H test was used to investi-gate the association of CK2β expression with clinical features. The Kaplan-Meier method was used for survival analysis, and the log-ranktest was used for comparison between groups. Results Western blot and real-time PCR showed that the expression rate of CK2β in HCCtissue was significantly higher than that in adjacent tissue, cirrhotic tissue, and normal liver tissue ( P < 0. 05) ; there was no significantdifference in the expression of CK2β between adjacent tissue and cirrhotic tissue ( P > 0. 05) , and the expression of CK2β in adjacent tissueand cirrhotic tissue was significantly higher than that in normal liver tissue ( P < 0. 05) . Immunohistochemical staining showed that there wasa significant difference in the positive rate of CK2β between HCC tissue and adjacent tissue in the 127 HCC patients ( 85. 8% vs 63. 0%, P < 0. 001) . There was a significant difference in CK2β expression distribution between HCC patients with different ages ( Z =-2. 277, P = 0. 023) , presence or absence of liver cirrhosis ( Z =-2. 144, P = 0. 032) , different tumor sizes ( Z =-2. 289, P = 0. 004) , or differ-ent Edmondson-Steiner pathological grades ( χ2= 8. 210, P = 0. 016) . The Kaplan-Meier survival curve analysis showed that the stronglypositive CK2β expression group had a significantly shorter postoperative survival time than the moderately positive, weakly positive, and neg-ative CK2β expression groups ( all P < 0. 001) . Conclusion CK2β may be involved in the development and progression of HCC, and itspositive expression is associated with the prognosis of HCC patients.

     

  • loading
  • [1] CHEN W, ZHENG R, BAADE PD, et al. Cancer statistics inChina, 2015[J]. CA Cancer J Clin, 2016, 66 (2) :115-132.
    [2] National Health and Family Planning Commission of the People'sRepublic of China. Diagnosis, management, and treatment ofhepatocellular carcinoma (V2017) [J]. J Clin Hepatol, 2017, 33 (8) :1419-1431. (in Chinese) 中华人民共和国国家卫生和计划生育委员会.原发性肝癌诊疗规范 (2017年版) [J].临床肝胆病杂志, 2017, 33 (8) :1419-1431.
    [3] SHARIFF MI, COX IJ, GOMAA AI, et al. Hepatocellular carci-noma:Current trends in worldwide epidemiology, risk factors, diagnosis and therapeutics[J]. Expert Rev GastroenterolHepatol, 2009, 3 (4) :353-367.
    [4] DUNCAN JS, LITCHFIELD DW. Too much of a good thing:The role of protein kinase CK2 in tumorigenesis and prospectsfor therapeutic inhibition of CK2[J]. Biochim Biophys Acta, 2008, 1784 (1) :33-47.
    [5] RUZZENE M, PINNA LA. Addiction to protein kinase CK2:Acommon denominator of diverse cancer cells[J]. Biochim Bio-phys Acta, 2010, 1804 (3) :499-504.
    [6] KIM S, HAM S, YANG K, et al. Protein kinase CK2 activationis required for transforming growth factor beta-induced epi-thelial-mesenchymal transition[J]. Mol Oncol, 2018, 12 (10) :1811-1826.
    [7] GUERRA B, ISSINGER OG. Protein kinase CK2 and its role incellular proliferation, development and pathology[J]. Electro-phoresis, 2015, 20 (2) :391-408.
    [8] BROWN MS, DIALLO OT, HU M, et al. CK2 modulation of NF-kappaB, TP53 and the malignant phenotype in head andneck cancer by anti-CK2 oligonucleotides in vitro or in vivovia sub-50 nm nanocapsules[J]. Clin Cancer Res, 2010, 16 (8) :2295-2307.
    [9] BLIESATH J, HUSER N, OMORI M, et al. Combined inhibitionof EGFR and CK2 augments the attenuation of PI3K-Akt-m TOR signaling and the killing of cancer cells[J]. Cancer Let-ters, 2012, 322 (1) :113-118.
    [10] CHEN WY, REN N. Advances in molecular targeted therapyfor hepatocellular carcinoma[J]. J Clin Hepatol, 2018, 34 (7) :1387-1394. (in Chinese) 陈万勇, 任宁.肝细胞癌分子靶向治疗进展[J].临床肝胆病杂志, 2018, 34 (7) :1387-1394.
    [11] BUONTEMPO F, MCCUBREY JA, ORSINI E, et al. Therapeu-tic targeting of CK2 in acute and chronic leukemias[J]. Leu-kemia, 2017, 32 (1) :1-10.
    [12] GOWDA C, SACHDEV M, MUTHISAMI S, et al. Casein ki-naseⅡ (CK2) as a therapeutic target for hematological malig-nancies[J]. Curr Pharm Des, 2017, 23 (1) :95-107.
    [13] FILHOL O, NUEDA A, MARTEL V, et al. Live-cell fluores-cence imaging reveals the dynamics of protein kinase CK2 in-dividual subunits[J]. Mol Cell Biol, 2003, 23 (3) :975-987.
    [14] BIBBY AC, LITCHFIELD DW. The multiple personalities of theregulatory subunit of protein kinase CK2:CK2 dependent andCK2 independent roles reveal a secret identity for CK2beta[J]. Int J Biol Sci, 2005, 1 (2) :67-79.
    [15] GOLDEN D, CANTLEY LG. Casein kinase 2 prevents mesen-chymal transformation by maintaining Foxc2 in the cytoplasm[J]. Oncogene, 2015, 34 (36) :4702-4712.
    [16] DESHIERE A, DUCHEMINPELLETIER E, SPREUX E, et al.Unbalanced expression of CK2 kinase subunits is sufficient todrive epithelial-to-mesenchymal transition by Snail1 induc-tion[J]. Oncogene, 2013, 32 (11) :1373-1383.
    [17] VOLODINA YL, SHTIL AA. Casein kinase 2, a versatile regu-lator of cell surviva[J]. Mol Biol (Mosk) , 2012, 46 (3) :381-390.
    [18] BIBBY AC, LITCHFIELD DW. The multiple personalities of theregulatory subunit of protein kinase CK2:CK2 dependent andCK2 independent roles reveal a secret identity for CK2β[J]. IntJ Biol Sci, 2005, 1 (2) :67-79.
    [19] ZOU JJ, LUO HS, HUANG ZY, et al. Correlation of casein ki-nase 2βoverexpression to the metastatic ability of colorectalcancer cells in vitro[J]. J South Med Univ, 2011, 31 (4) :628-632. (in Chinese) 邹金金, 罗何三, 黄志勇, 等.高表达Ck2β与大肠癌发生和转移的相关性研究[J].南方医科大学学报, 2011, 31 (4) :628-632.
    [20] CHEN B, CAO ZY, CAO CH, et al. Effect of casein kinase 2βin esophageal carcinoma and its clinical significance[J]. JSouth Med Univ, 2012, 32 (10) :1491-1494, 1497. (in Chi-nese) 陈勃, 曹忠宜, 曹传辉, 等.蛋白激酶CK2β在食管癌中的表达及其临床意义[J].南方医科大学学报, 2012, 32 (10) :1491-1494, 1497.
    [21] VILARDELL J, ALCARAZ E, SARRE, et al. Under-expres-sion of CK2βsubunit in ccRCC represents a complementarybiomarker of p-STAT3 Ser727 that correlates with patient sur-vival[J]. Oncotarget, 2018, 9 (5) :5736-5751.
    [22] LIN KY, FANG CL, CHEN Y, et al. Overexpression of nuclearprotein kinase CK2 Beta subunit and prognosis in human gas-tric carcinoma[J]. Ann Surg Oncol, 2010, 17 (6) :1695-1702.
    [23] FILHOL O, GIACOSA S, WALLEZ Y, et al. Protein kinase CK2in breast cancer:The CK2βregulatory subunit takes centerstage in epithelial plasticity[J]. Cell Mol Life Sci, 2015, 72 (17) :3305-3322.
    [24] KIM S, HAM S, YANG K, et al. Protein kinase CK2 activationis required for transforming growth factorβ-induced epithelial-mesenchymal transition[J]. Mol Oncol, 2018, 12 (10) :1811-1826.
    [25] MIKULITS W. Epithelial to mesenchymal transition in hepato-cellular carcinoma[J]. Future Oncol, 2018, 5 (8) :1169.
  • 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

    Article Metrics

    Article views (1395) PDF downloads(295) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return