肝细胞癌组织HBXIP和GRIM-19表达及意义的探讨
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摘要
目的探讨乙肝病毒X蛋白结合蛋白HBXIP和细胞凋亡调节因子GRIM-19在肝细胞癌组织中的表达及意义。方法收集42例肝细胞癌组织和28例正常肝脏组织,采用免疫组织化学法检测两种组织中HBXIP和GRIM-19的表达。结果在肝细胞癌组织和正常肝脏组织中,HBXIP阳性表达率分别为80.95%(34/42)和42.86%(12/28);而GRIM-19阳性表达率分别为40.48%(17/42)和75.00%(21/28),差异有统计学意义(P<0.01)。肝细胞癌组织中HBXIP的阳性表达率在低、未分化和Ⅲ~Ⅳ期的表达水平高于高、中分化和Ⅰ~Ⅱ期组织;而GRIM-19的阳性表达率与之相反,且无门脉癌栓组织中GRIM-19的阳性表达率高于有门脉癌栓组织。HBXIP与GRIM-19表达呈负相关(r_s=-0.400,P<0.01)。结论 HBXIP和GRIM-19的异常表达可能与肝细胞癌的发生及浸润转移有密切关系。
Objective To investigate the expressions of HBXIP and GRIM-19 in hepatocellular carcinoma tissues and their clinic significance.Methods Hepatocellular carcinoma tissue(n=42) and normal liver tissue(n=28) were collected from Tianjin First Central Hospital,immunohistochemistry was used to detect the expressions of HBXIP and GRIM- 19 in these two groups.Results Rate of cells with positive expressions of HBXIP in hepatocellular carcinoma and normal liver tissues were 80.95%(34/42) and 42.86%(l2/28)respectively;Rate of cells with positive expression of GRIM-19 in hepatocellular carcinoma tissues and normal liver tissues was 40.48%(17/42) and 75.00%(21/28)respectively,and the difference between these two groups was statistically significant(P < 0.05);The expression of HBXIP was higher but the expression of GRIM-19 was lower in poor differentiated and stage Ⅲ-Ⅳ cells than those in well and moderate differentiated cells and in stage Ⅰ-Ⅱ,cells.What's more,the expression of GRIM-19 is higher in tissue without portal thrombosis than that in tissue with portal thrombosis.The expression of HBXIP was negatively correlated with GRIM-19 expression(r_s=-0.400,P < 0.01).Conclusion The abnormal expressions of HBXIP and GRIM- 19 may play important roles in the process of development and metastasis of hepatocellular carcinoma.
Objective To investigate the expressions of HBXIP and GRIM-19 in hepatocellular carcinoma tissues and their clinic significance.Methods Hepatocellular carcinoma tissue(n=42) and normal liver tissue(n=28) were collected from Tianjin First Central Hospital,immunohistochemistry was used to detect the expressions of HBXIP and GRIM- 19 in these two groups.Results Rate of cells with positive expressions of HBXIP in hepatocellular carcinoma and normal liver tissues were 80.95%(34/42) and 42.86%(l2/28)respectively;Rate of cells with positive expression of GRIM-19 in hepatocellular carcinoma tissues and normal liver tissues was 40.48%(17/42) and 75.00%(21/28)respectively,and the difference between these two groups was statistically significant(P < 0.05);The expression of HBXIP was higher but the expression of GRIM-19 was lower in poor differentiated and stage Ⅲ-Ⅳ cells than those in well and moderate differentiated cells and in stage Ⅰ-Ⅱ,cells.What's more,the expression of GRIM-19 is higher in tissue without portal thrombosis than that in tissue with portal thrombosis.The expression of HBXIP was negatively correlated with GRIM-19 expression(r_s=-0.400,P < 0.01).Conclusion The abnormal expressions of HBXIP and GRIM- 19 may play important roles in the process of development and metastasis of hepatocellular carcinoma.
引文
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[13]Angell JE,Lindner DJ,Shapiro PS,et al.Identification of GRIM-19,a novel cell death-regulatory gene induced by the interferon-be-ta and retinoic acid combination,using a genetic approach[J].J BiolChem,2000,275(43):33416-33426.
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[15]Zhou AM,Zhao JJ,Ye J,et al.Expression and clinical significanceof GRIM-19 in non-smal I celllung cancer[J].Chinese Journal ofCancer,2009,28(4):431-435.[周爱民,赵继京,叶静,等.GRIM-19蛋白在非小细胞肺癌组织中的表达及其临床意义[J].癌症,2009,28(4):431-435].
[16]Cheng Y,Zhou Y,Wei Y,et al.Study of effect sofexpression ofGRIM-19 on invasion and apoptosis of cervical cancercell xeno-graft tumor[J].Chin J Lab Diagn,2010,14(5):733-735.[程勇,周颖,卫莹,等.GRIM-19的表达对人子宫颈癌细胞移植瘤细胞侵袭、凋亡的影响研究[J].中国实验诊断学,2010,14(5):733-735].
[2]Kordestani R,Mirshafiee H,Hosseini SM,et al.Effect of hepatitis Bvirus X gene on the expression level of p53 gene using hep G2 cellline[J].Avicenna J Med Biotechnol,2014,6(1):3-9.
[3]Liu F,You X,Wang Y,et al.The oncoprotein HBXIP enhances an-giogenesis and growth of breast cancer through modulating FGF8and VEGF[J].Carcinogenesis,2014,35(5):1144-1153.doi:10.1093/carcin/bgu021.
[4]Wang FZ,Sha L,Qiao L,et al.Promotion of transcriptional activityof NF-κB mediated by HBXIP in Hepatoma Cells[J].Progress inBiochemistry and Biohysics,2007,34(11):1197-1201.[王凤泽,沙丽,乔玲,等.乙肝病毒X蛋白结合蛋白(HBXIP)增强肝癌细胞NF-κB转录活性的实验研究[J].生物化学与生物物理进展,2007,34(11):1197-1201].
[5]Zhou Y,Ling B.Functions of GRIM-19 and its association with tu-mors[J].J Med Mol Biol,2008,5(3):262-264.[周颖,凌斌.GRIM-19的功能及与肿瘤的相关性[J].医学分子生物学杂志,2008,5(3):262-264].
[6]Zhao JL,Li SP,Wang FF,et al.Approach on expression and clini-cal significance of KISS-1 and E-cadherin in hepatocellular carci-noma[J].Chin J Cancer Prev Treat,2013,20(13):995-997.[赵建龙,李世朋,王朏朏,等.肝细胞癌组织KISS-1和E-cadherin表达临床意义的探讨[J].中华肿瘤防治杂志,2013,20(13):995-997].
[7]Wang YF,Lin Z,Lu Q,et al.The expressions of musashi-2 andCD133 protein in colonic adenocarcinoma[J].Tianjin Med J,2013,41(12):1153-1155.[王娅菲,林中,卢青,等.Musashi-2、CD133在结肠腺癌中的表达[J].天津医药,2013,41(12):1153-1155].
[8]Marusawa H,Matsuzawa S,Welsh K,et al.HBXIP functions as a co-factor of survivin in apoptosis suppression[J].EMBO J,2003,22(11):2729-2740.
[9]Wang FZ,Sha L,Zhang WY,et al.Involvement of hepatitis B X-in-teracting protein(HBXIP)in proliferation regulation of cells[J].Ac-ta Pharmacol Sin,2007,28(3):431-438.
[10]Liu Q,Bai X,Li H,et al.The oncoprotein HBXIP upregulatesLin28B via activating TF II D to promote proliferation of breast can-cer cells[J].Int J Cancer,2013,133(6):1310-1322.doi:10.1002/ijc.28154.
[11]Xu F,You X,Liu F,et al.The oncoprotein HBXIP up-regulatesSkp2 via activating transcription factor E2F1 to promote prolifera-tion of breast cancer cells[J].Cancer Lett,2013,333(1):124-132.doi:10.1016/j.canlet.2013.01.029.
[12]Yue L,Li L,Liu F,et al.The oncoprotein HBXIP activates tran-scriptional coregulatory protein LMO4 via Sp1 to promote prolifera-tion of breast cancer cells[J].Carcinogenesis,2013,34(4):927-935.doi:10.1093/carcin/bgs399.
[13]Angell JE,Lindner DJ,Shapiro PS,et al.Identification of GRIM-19,a novel cell death-regulatory gene induced by the interferon-be-ta and retinoic acid combination,using a genetic approach[J].J BiolChem,2000,275(43):33416-33426.
[14]Zhou Y,Wei Y,Li M,et al.Effects of expression of GRIM-19 on pro-liferation of cervical cancer cell line He La[J].Tumor,2009(10):940-943.[周颖,卫莹,李敏,等.GRIM-19表达对子宫颈癌He La细胞增殖的影响[J].肿瘤,2009(10):940-943].
[15]Zhou AM,Zhao JJ,Ye J,et al.Expression and clinical significanceof GRIM-19 in non-smal I celllung cancer[J].Chinese Journal ofCancer,2009,28(4):431-435.[周爱民,赵继京,叶静,等.GRIM-19蛋白在非小细胞肺癌组织中的表达及其临床意义[J].癌症,2009,28(4):431-435].
[16]Cheng Y,Zhou Y,Wei Y,et al.Study of effect sofexpression ofGRIM-19 on invasion and apoptosis of cervical cancercell xeno-graft tumor[J].Chin J Lab Diagn,2010,14(5):733-735.[程勇,周颖,卫莹,等.GRIM-19的表达对人子宫颈癌细胞移植瘤细胞侵袭、凋亡的影响研究[J].中国实验诊断学,2010,14(5):733-735].