蛋白激酶CK2β在肝细胞癌中的表达及临床意义

梁润威; 范正军; 黄娟; 孙涛; 余祖启

doi:10.3969/j.issn.1001-5256.2019.03.019

蛋白激酶CK2β在肝细胞癌中的表达及临床意义

DOI: 10.3969/j.issn.1001-5256.2019.03.019

郑州大学第一附属医院肝胆胰外科

基金项目:

河南省科技攻关项目(182102310143)；

详细信息

中图分类号: R735.7
计量
- 文章访问数: 1395
- HTML全文浏览量: 15
- PDF下载量: 295
- 被引次数: 0
出版历程
- 收稿日期: 2018-10-24
- 出版日期: 2019-03-20

Expression and clinical significance of protein kinase CK2β in hepatocellular carcinoma

Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of Zhengzhou University

Research funding:

摘要

摘要: 目的研究蛋白激酶CK2β在肝细胞癌组织中的表达及临床意义,并探讨其表达与患者预后的关系。方法收集2012年1月-2013年6月于郑州大学第一附属医院肝胆胰外科确诊的127例肝细胞癌患者癌组织及癌旁组织,采用免疫组化法检测其CK2β的表达,分析癌组织中CK2β表达强度与肝癌患者临床特征的关系。另收集本院2018年3-6月期间手术切除的20例肝细胞癌癌组织、癌旁组织、肝硬化组织、正常肝组织标本并提取蛋白和mRNA,运用Westen Blot和real-time PCR检测其CK2β表达情况。多组间均数比较采用单因素方差分析,进一步两两比较采用Bonferroni检验,计数资料组间比较采用χ2检验。CK2β在肝细胞癌的表达差异与临床特征参数的关系采用Mann-Whitney U检验或Kruskal-Wallis H检验。生存分析采用Kaplan-Meier法,组间比较采用log-rank检验。结果 Westen Blot和real-time PCR结果证实CK2β在癌组织中表达率显著高于癌旁组织、肝硬化组织和正常肝组织（P值均<0. 05）;癌旁及肝硬化组织中CK2β表达无差异（P值均...
- 癌,肝细胞 /
- 蛋白质丝氨酸苏氨酸激酶 /
- 预后
Abstract: 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.
- carcinoma, hepatocellular /
- protein-serine-threonine kinases /
- prognosis

HTML全文

参考文献(25)

[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.

施引文献

资源附件(0)

访问统计