王露,何常,胡斌,李珀
WANG Lu,HE Chang,HU Bin,LI Po

• 1:贵州医科大学病理学教研室
• 2:贵州医科大学附院病理科

摘要(Abstract)：

目的:探讨结直肠癌(CRC)组织内Nek8、BICD2及VHL蛋白表达与其生物学行为和预后的关系。方法:取30例CRC患者的癌组织及配对邻近的正常黏膜组织,20例结直肠黏膜慢性炎症组织、20例结直肠管状腺瘤及60例结直肠管状腺癌(II级)切片标本,应用免疫组化SP法检测Nek8、BICD2及VHL蛋白表达水平,Spearman分析Nek8、BICD2和VHL表达水平与CRC组织、结直肠管状腺瘤组织和慢性炎症组织的相关性,分析Nek8、BICD2和VHL表达水平与CRC临床病理参数的关系。结果:在30例配对标本中,Nek8和BICD2在CRC组织中高表达(56.7%、76.7%)明显高于配对的正常黏膜组织(13.3%、13.3%),而VHL在癌组织中的表达(30.0%)明显低于配对的正常黏膜组织(63.3%,P<0.05);Nek8和BICD2在CRC组织(83.3%、73.3%)及腺瘤组织(80.0%、75.0%)阳性率高于结直肠黏膜慢性炎症组织(25.0%、20.0%,P<0.05);VHL在癌组织(26.7%)、腺瘤组织(40.0%)及慢性炎症组织(75.0%)中的阳性表达呈逐渐增加的趋势(P<0.05)Nek8、BICD2和VHL的表达水平与CRC患者性别、年龄、浸润深度、临床分期、淋巴转移、5年生存率及远处转移无关(P>0.05);Spearman相关分析结果显示,CRC组织中Nek8与BICD2表达呈正相关(r=0.337,P<0.05),Nek8和BICD2与VHL间无相关性(P>0.05)。结论:在CRC组织中Nek8、BICD2表达上调,VHL表达下调,三者可能参与了CRC的发生和发展。
Objective: To investigate the expression of Nek8,BICD2 and VHL in colorectal carcinoma tissues and significance in prognosis of CRC. Methods: 30 cases of colorectal carcinoma tissues and paired adjacent normal mucosa tissues,20 cases of colorectal chronic inflammation tissues,20 cases of colorectal tubular adenoma tissues and 60 cases of colorectal tubular adenocarcinoma section preparation( level two) were collected. IHC SP method was adopted to determine Nek8,BICD2 and VHL proteins expression. Spearman was adopted to analyze the correlation between the expression level of Nek8,BICD2 and VHL and colorectal carcinoma tissues,colorectal tubular adenoma tissues and chronic inflammation tissues,and analyze the relationship between the expression of Nek8,BICD2 and VHL and CRC clinical pathologic parameters. Results: In the 30 paired samples,Nek8 and BICD2 were highly expressed in CRC tissues( 56. 7%,76. 7%),significantly higher than that in normal mucosa tissues( 13. 3%,13. 3%),while the expression of VHL in cancer tissues( 30%) was significantly lower than that in paired normal mucosa tissues( 63. 3%)( P < 0. 05); The positive expression rates of Nek8 and BICD2 proteins in colorectal adenocarcinoma tissues( 83. 3%,73. 3%) and colorectal adenoma tissues( 80. 0%,75. 0%) were significantly higher than those in chronic inflammation tissues( 25. 0%,20. 0%,P < 0. 05). There existed a gradually increased tendency about the positive expression of VHL protein in cancer tissues( 26. 7%),adenomas( 40%) and chronic inflammation( 75%,P < 0. 05). There were no correlation between protein expression level of Nek8,BICD2 and VHL and CRC patients' sex,age,infiltration degree,clinical stage,lymph node metastasis,five year survival rate and metastasis( P > 0. 05). Spearman correlation analysis showed that there was a positive correlation between the expression of Nek8 and BICD2 in CRC tissues( r = 0. 337,P < 0. 05).There was no correlation between Nek8 and BICD2 and VHL( P > 0. 05). Conclusion: Nek8 and BICD2 expression up regulate,VHL expression down regulate,which may be involved in the occurreme and development of CRC.

关键词(KeyWords)： 免疫组织化学;结直肠肿瘤;蛋白;Nek8;BICD2;VHL
immunohistochemistry;colorectal neoplasm;protein;Nek8;BICD2;VHL

Abstract:

Keywords:

基金项目(Foundation): 贵州省科技厅基金(E2014-4)

作者(Author): 王露,何常,胡斌,李珀
WANG Lu,HE Chang,HU Bin,LI Po

DOI: 10.19367/j.cnki.1000-2707.2017.04.017

参考文献(References)：

• [1]Favoriti P,Carbone G,Greco M,et al.Worldwide burden of colorectal cancer:a review[J].Updates in Surgery,2016(1):7-11.
• [2]Siegel R,Desantis C,Jemal A.Colorectal cancer statistics,2014[J].Ca A Cancer Journal for Clinicians,2014(2):104-117.
• [3]Torre LA,Bray F,Siegel RL,et al.Global cancer statistics,2012[J].Ca A Cancer Journal for Clinicians,2015(2):87-108.
• [4]李鹏,王拥军,陈光勇,等.中国早期结直肠癌及癌前病变筛查与诊治共识[J].中国实用内科杂志,2015(3):211-227.
• [5]程璘令,刘雅雅,苏柱泉,等.慢性阻塞性肺疾病-哮喘重叠综合征慢性阻塞性肺疾病和支气管哮喘临床特征差异研究[J].中国实用内科杂志,2015(2):143-145.
• [6]Fry AM,O'Regan L,Sabir SR,et al.Cell cycle regulation by the NEK family of protein kinases.[J].Journal of Cell Science,2012(19):4423-4433.
• [7]Bowers AJ,Boylan JF.Nek8,a NIMA family kinase member,is overexpressed in primary human breast tumors[J].Gene,2004(2):135-142.
• [8]Liu Y,Salter HK,Holding AN,et al.Bicaudal-D uses a parallel,homodimeric coiled coil with heterotypic registry to coordinate recruitment of cargos to dynein.[J].Genes&Development,2013(11):1233-1246.
• [9]Terenzio M,Schiavo G.The more,the better:the BICD family gets bigger[J].Embo Journal,2010(10):1625-1626.
• [10]Holland PM,Milne A,Garka K,et al.Purification,cloning,and characterization of Nek8,a novel NIMArelated kinase,and its candidate substrate Bicd2[J].Journal of Biological Chemistry,2002(18):16229-16240.
• [11]Grubb RL,Choyke PL,Pinto PA.Management of von Hippel-Lindau-associated kidney cancer[J].Nature Clinical Practice Urology,2005(5):248-255.
• [12]Fukasawa K.Centrosome amplification,chromosome instability and cancer development[J].Cancer Letters,2005(1):6-19.
• [13]Kumar A,Rajendran V,Sethumadhavan R,et al.Role of centrosome in regulating immune response[J].Current Drug Targets,2014(5):558-563.
• [14]Francia ME,Striepen B.Cell division in apicomplexan parasites.[J].Nature Reviews Microbiology,2014(2):125-136.
• [15]Chan WL,Yuo CY,Yang WK,et al.Transcribed pseudogeneψPPM1K generates endogenous siRNA to suppress oncogenic cell growth in hepatocellular carcinoma[J].Nucleic Acids Research,2013(6):3734-3747.
• [16]郭亚平,朱红,付茂勇,等.Nek8在食管鳞癌中的表达及意义[J].重庆医学,2015(5):597-599.
• [17]Jr KW.The von Hippel-Lindau tumour suppressor protein:O2 sensing and cancer.[J].Nature Reviews Cancer,2008(8):865-873.
• [18]Ding XF,Zhou J,Hu QY,et al.The tumor suppressor p VHL down-regulates never-in-mitosis A-related kinase 8 via hypoxia-inducible factors to maintain cilia in human renal cancer cells[J].Journal of Biological Chemistry,2015(3):1389-1394.

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