肝细胞癌组织SOCS1和STAT3蛋白的表达意义

目的:探讨SOCS1和STAT3蛋白在HCC组织中的表达、相互关系及在HCC发生发展中的意义.方法:应用免疫组化方法检测48例HCC组织和癌周肝组织、肝硬化(liver cirrhosis,LC)组织(n=11)及正常肝组织中(n=11)SOCS1和STAT3的表达水平.结果:癌周肝组织中SOCS1蛋白表达强度显著高于HCC组织,SOCS1蛋白在LC组织及正常肝组织中全部呈阴性表达.HCC组织和癌周肝组织STAT3蛋白阳性表达率显著高于LC组织和正常肝组织;SOCS1在瘤体大小间的表达有显著性差异(P<0.01).STAT3在表达AFP阴性和阳性癌组织组间有显著性差异(P<0.05).HCC组织中SOCS1和STAT3表达具有显著等级正相关(rs=0.431,P<0.01).结论:SOCS1和STAT3表达与HCC的发生密切相关,且两者之间的表达强度具有显著等级正相关.     

WEE1与肝癌的关系

目的:探讨WEE1在肝细胞癌(HCC)发生、发展中的异常表达及与肿瘤病理分期的关系.方法:收集2010-03/2010-05河南省人民医院肝胆外科手术标本正常肝组织23例,肝硬化20例,HCC42例.采用RT-PCR检测mRNA水平的表达,Western blot及免疫组织化学检测蛋白的表达,并分析其与肝癌临床病理学分期的关系.结果:WEE1mRNA阳性表达率分别为21.7%、55.0%和90.5%,三组间差异有统计学意义(P<0.01).Western blot和免疫组织化学方法分别检测蛋白阳性表达率分别为13.04%/17.4%、40%/60%和78.6%/83.3%,三组间相比差异有统计学意义(P<0.01).肝癌组织中WEE1强度与肿瘤的分化程度及病理分级相关(χ2=17.454,P<0.01;χ2=14.559,P<0.01).结论:WEE1基因在肝癌中呈上调表达,其参与的DNA的修复异常与肝癌的发生密切相关; 且与肿瘤的分化程度和病理分级相关.     

GADD45β在肝癌中的异常表达

目的:探讨生长抑制DNA损伤诱导因子β(GADD45β)与肝细胞癌(hepatocellular carcinoma,HCC)发生、发展的关系.方法:应用寡核苷酸基因芯片、反转录PCR(RT-PCR)、免疫组织化学技术检测GADD45β在人正常肝组织、肝硬化组织和肝癌组织中的异常表达,分析GADD45β与临床病理学特征的关系及其异常表达的可能分子生物学机制.结果:正常肝组织、肝硬化组织和肝癌组织中GADD45β mRNA的阳性表达率分别为80％、60％和26％,肝癌组织与正常肝组织间有非常统计学差异(x2=15.128,P<0.01); GADD45β在肝癌组织中的表达缺失与病理学分级显著相关(P<0.01).结论:GADD45β作为抑癌基因在肝癌的发生发展中起到相当重要的作用,且与肿瘤分化程度密切相关.     

肿瘤拒绝抗原1在肝硬化和肝癌组织中的表达及其与肝癌临床病理学特征的关系

目的 探讨肿瘤拒绝抗原1(TRA1)在肝细胞癌(HCC)和肝硬化组织中的表达水平及其与HCC临床病理学特征的关系.方法 采用RT-PCR法、Western blot和免疫组织化学法分别检测了HCC和肝硬化组织中TRA1 mRNA和蛋白的表达水平,并与HCC临床病理学特征进行相关分析.RT-PCR和Western blot结果采用单因素方差分析;免疫组织化学结果分析采用Fisher's确切概率法;相关性分析采用Spearman等级相关.结果 经对RT-PCR结果分析,HCC和肝硬化组织中TRA1 mRNA表达水平高于正常肝组织水平(F值分别为20.821和12.311,P值均＜0.05).Western blot检测结果显示,HCC和肝硬化组织中TRA1蛋白表达水平也高于正常肝组织(F值分别为21.231和20.125,P值均＜0.05).经免疫组织化学分析,TRA1蛋白在正常对照组、肝硬化组和HCC组的表达逐渐增强,阳性表达率分别为57.14%、78.95%和93.75%.其表达水平与HCC分化程度呈负相关(r=-0.4655,P＜0.01);与HCC患者TNM分期呈正相关(r=0.5157,P＜0.01).结论 TRA1在肝硬化和HCC中的过表达可能与肝癌的发生和发展有关,并有可能成为一个潜在的HCC早期诊断标志物;TRA1的检测有助于判断HCC的分化程度,与HBV的感染有一定关系,同时可作为判断预后的指标.     

GADD45β在肝癌中的异常表达

目的: 探讨生长抑制DNA损伤诱导因子beta(GADD45beta)与肝细胞癌(hepatocellular carcinoma, HCC)发生、发展的关系. 方法: 应用寡核苷酸基因芯片、反转录PCR(RT-PCR)、免疫组织化学技术检测GADD45beta在人正常肝组织、肝硬化组织和肝癌组织中的异常表达, 分析GADD45beta与临床病理学特征的关系及其异常表达的可能分子生物学机制. 结果: 正常肝组织、肝硬化组织和肝癌组织中GADD45beta mRNA的阳性表达率分别为80%、60%和26%, 肝癌组织与正常肝组织间有非常统计学差异(chi2 = 15.128, P<0.01); GADD45β蛋白的阳性表达率在正常肝组织、肝硬化组织和肝癌组织中分别为85%、70%和31%, 有显著统计学差异(chi2 = 24.619, P<0.01). GADD45beta在肝癌组织中的表达缺失与病理学分级显著相关(P<0.01). 结论: GADD45beta作为抑癌基因在肝癌的发生发展中起到相当重要的作用, 且与肿瘤分化程度密切相关.     

原发性肝癌组织芯片中乙酰肝素酶的表达及意义

目的:探讨乙酰肝素酶(heparanase,HPA)蛋白在原发性肝细胞癌(HCC)组织芯片中的过度表达及临床意义.方法:125例HCC患者肝组织、48例肝癌患者癌旁组织、62例肝硬化患者肝组织及23例肝血管瘤患者相应正常肝组织构建组织微阵列.应用免疫组织化学检测HPA蛋白的表达水平,并分析其与HCC临床病理特征的关系.结果:HCC组织中的HPA蛋白的阳性率45.83%明显高于癌旁组织27.08%(x~2=2.23,P<0.05),肝硬化6.45%(x~2=5.262,P<0.05)和正常肝组织4.35%(x~2=3.895,P<0.05).癌旁组织中的HPA蛋白阳性率明显高于肝硬化(x~2=2.882,P<0.05)及正常肝组织(x~2=2.361,P<0.05);HCC中临床TNM分期ⅠⅡ期HPA阳性率明显低于ⅢⅣ期(29.41% vs 67.31%,x~2 =4.111,P<0.05);HCC中无转移组HPA阳性率明显低于转移组(14.71% vs 63.33%,x~2= 3.978,P<0.05);HPA表达率在AFP≥400μg/L和AFP<400μg/L组(52.05% vs 36.17%,x~2= 2.071,P<0.05)、有无门脉癌栓组(71.74% vs 29.73%,x~2=4.472,P<0.05)、多个和单个肿瘤结节组(73.91% vs 28.38%,x~2=4.847,P<0.05)以及肿瘤直径≥5 cm和<5 cm组(57.89% vs 25%,x~2=3.471,P<0.01)分别具有显著性意义.HPA表达与年龄、性别、分化程度、有无肝硬化及肿瘤包膜浸润无关.结论:HPA高表达在HCC的发生、发展及转移中起重要作用.检测HPA蛋白指标有助于HCC诊断和判断患者预后.     

Beclin1和NF-κB p65在肝癌中的表达及其临床意义

目的:分析自噬基因Beclin1和核因子NF-κB(nuclear factor-kappaB,NF-κB)在原发性肝细胞性肝癌(primary human hepatocellular carcinoma,HCC)中的表达及其临床意义.方法:收集顺德第一人民医院2003-01/2007-12手术切除经病理学证实的HCC50例,肝炎后肝硬化手术切除或活检标本30例,肝炎患者肝脏穿刺组织30例和正常肝组织10例.应用免疫组化S-P法检测肝脏组织中Beclin1和NF-κB p65蛋白的表达.结果:原发性肝细胞性肝癌、肝硬化、肝炎和正常肝组织的BeClin1蛋白阳性表达率分别是78.00%(39/501、26.67%(8/30)、53.33%(16/30)、10.00%(1/10),四者之间的差异有统计学意义(χ2=28.31,P<0.05),且Beclinl在原发性肝细胞性肝癌组织表达明显高于在肝硬化组织,肝炎组织,正常肝组织中的表达(χ2=20.39,5.31,14.41,P<0.05);在肝炎组织表达明显高于在肝硬化组织.正常肝组织中的表达(χ2=4.44,χ2=4.12,P<0.05).原发性肝细胞性肝癌、肝硬化、肝炎和正常肝组织的NF-κB p65蛋白阳性表达率分别是74.00%(37/50)、36.67%(11/30)、30.00%(9/30)、20.00%(2/10),四者之间的差异有统计学意义(χ2=22.00,P<0.05),且NF-κB p65在原发性肝细胞性肝癌组织表达明显高于在肝硬化组织,肝炎组织,正常肝组织中的表达(χ2=10.89,χ2=14.85,χ2=8.44.P<0.05).结论:Beelin1和NF-κB p65在HCC中的表达关系密切,呈正相关;Beclin1和NF-κB p65异常表达与HCC的发展密切相关,在HCC的发展过程中起重要的作用.     

C-fos、EGFR在肝癌、肝硬化中表达的研究

目的 研究转录因子C-fos在人肝细胞癌(HCC)组织与肝硬化组织中的表达及C-fos与EGFR在HCC组织中表达的关系.方法 用免疫组化法检测51例HCC组织、51例癌旁组织、15例肝硬化组织、10例良性病变而切除的正常肝组织C-fos蛋白表达情况;EGFR在47例HCC组织中的表达情况.结果 C-fos蛋白在正常肝组织、肝硬化组织、肝癌组织中具有不同的表达,与肝病的不同进展情况存在显著差异(P<0.05),在HCC组织中C-fos蛋白表达与EGFR的表达无显著相关性(P>0.05).结论 C-fos蛋白在肝癌、肝硬化组织的过表达提示C-fos参与在肝癌、肝硬化的发病过程,但可能通过EGFR以外的信号通路参与肝癌发病过程.     

OPN和Syndecan-1在原发性肝癌中的表达及与临床病理参数之间的相关性

目的:应用组织芯片技术考察骨桥蛋白(osteopontin,OPN)和Syndecan-1在原发性肝细胞癌(hepatocellular carcinoma,HCC)中的表达及与临床病理参数之间的相关性,分析两者在HCC发生发展过程中的可能机制.方法:应用S-P法对高通量肝癌组织芯片(478点阵,产品批号:OD-CT-DgLiv01-001)进行染色,检测OPN和Syndecan-1蛋白在肝癌、肝硬化和正常肝组织中的表达.结果:OPN在HCC、肝硬化和正常肝组织中的阳性率分别为73.3%,47.4%和22.2%,差异具有显著性(P<0.05,P<0.05);Syndecan-1在HCC、肝硬化和正常肝组织中的阳性率分别为19.6%,35.0%和90%,亦有显著性差异(P<0.05,P<0.01).单因素分析结果显示OPN的表达与肿瘤包膜的完整性(x~2=4.52,P<0.05),门静脉有无癌栓(x~2=4.28,P<0.05)及肿瘤的转移相关(x~2=7.21,P<0.05),与其他临床病理特征没有相关性;Syndecan-1的表达与肿瘤有无包膜(x~2=5.58,P<0.01),病理分级(x~2=4.35,P<0.01)以及肿瘤转移与否相关(x~2=3.37,P<0.05),与其他临床病理特征没有相关性.蛋白之间的相关性分析显示,OPN与Syndecan-1之间存在负相关(r=-0.439,P<0.01).结论:组织芯片是一种可高效率和高通量研究肿瘤分子病理的技术平台;HCC的发生发展与癌细胞OPN的过表达和Syndecan-1表达下调可能有关,OPN可能通过下调Syndecan-1的表达,降低肿瘤细胞之间的黏附性,从而促进肿瘤的转移.     

EIF-5A2在肝细胞癌中的表达及其与VEGF、MVD的关系

目的:探讨真核翻译起始因子-5A2(eukaryotic initiation factor 5A2,EIF-5A2)在肝癌内的表达及其与VEGF表达、血管密度和临床病理指标的关系.方法:用免疫组织化学方法检测49例HCC组织及6例正常肝组织中EIF-5A2、VEGF和CD34的表达,计数微血管密度(MVD),并结合临床病理特征进行比较分析.结果:49例HCC组织中EIF-5A2、VEGF、CD34阳性表达率分别为87.7%、89.7%及100.0%,正常肝组织EIF-5A2、CD34表达呈阴性,VEGF表达为阴性或弱阳性.肝癌组织中EIF-5A2蛋白表达与VEGF表达及MVD间均呈正相关(r=0.416,0.321,均P<0.05);不同肿瘤灶数量的HCC组织EIF-5A2、VEGF蛋白表达及MVD差别无显著性,不同直径HCC的EIF-5A2、VEGF蛋白表达差别亦无显著性,而不同直径的HCC的MVD差别有显著性(P<0.05).有癌栓形成组与无癌栓组相比EIF-5A2、VEGF蛋白表达及MVD差别均有显著性(均P<0.05).肿瘤包膜完整组与无胞膜/包膜不完整组两组间EIF-5A2、VEGF蛋白表达及MVD差别均有显著性(均P<0.05).结论:肝癌组织中有较高的EIF-5A2阳性表达;EIF-5A2表达与VEGF表达及MVD呈正相关,与HCC组织血管侵犯和转移倾向有关.     

巨噬细胞移动抑制因子和细胞周期蛋白D1的表达与肝细胞癌生长和转移的关系

目的研究巨噬细胞移动抑制因子（MIF）、细胞周期蛋白D1（Cyclin D1）、细胞周期蛋白依赖激酶4（CDK4）、磷酸化视网膜母细胞瘤易感基因产物蛋白（phospho—Rb）在HeC组织中的表达及其与癌细胞生长和转移的关系。方法应用组织芯片技术和免疫组织化学方法检测93份HCC组织中MIF、Cyclin D1、CDK4和phospho—Rb的表达，分析它们的表达与HCC临床病理特征的关系。结果93份HCC组织中MIF、Cyclin D1、CDK4和phospho—Rb的表达率分别为71％、41％、82％和14％，MIF和Cyclin D1阳性表达率与正常肝脏组织表达率之间的差异有统计学意义（P〈0．01），CDK4和phospho—Rb阳性表达率与正常肝脏组织表达率之间的差异无统计学意义（P〉0．05）。在≥3．5cm的肿瘤中MIF表达率为79％，明显高于在〈3．5cm肿瘤中的表达率48％（P〈0．01）；有转移的肝癌组织中Cyclin D1阳性率为62％，明显高于无转移组织中的阳性率35％，差异有统计学意义（P〈0．05）。MIF表达强弱与Cyclin D1的表达呈正相关关系（P〈0，01）。CDK4和phospho—Rb的表达与肿瘤大小及是否转移的关系无统计学意义。结论MIF和Cyclin D1在HCC发展进程中可能促进肿瘤的生长和转移。     

Activation of cyclin-dependent kinases CDC2 and CDK2 in hepatocellular carcinoma

BACKGROUND: The cyclin-dependent kinases (CDKs) CDC2 and CDK2 are key regulators of the cell cycle. The expression of the CDK alone does not necessary reflect their true activities because they are highly regulated by post-translational mechanisms. Human hepatocellular carcinoma (HCC) is one of the most common cancers in the world, but the kinase activities of CDKs in HCC have not been examined. METHODS: Here we examined the protein expression and kinase activities associated with CDC2 and CDK2 in HCC and the corresponding non-tumorous liver tissues. RESULTS: CDC2 and CDK2 are activated in HCC in over 70% and 80% of the cases, respectively, but have little correlation with clinical parameters and PCNA expression. Interestingly, PCNA was readily detectable in extracts from non-tumorous liver, but more than 60% of samples contain higher concentration of PCNA in HCC than the corresponding non-tumorous tissues. CDC2 and CDK2 are generally activated in the same HCC samples, but the extent of their activation varied significantly, suggesting that the pathways leading to the activation of CDC2 and CDK2 can be regulated independently. Both positive regulators of CDK activity like cyclins and CDKs, and negative regulators of CDK activity like p21(CIP1/WAF1) and Thr14/Tyr15 phosphorylation were up-regulated in HCC. CONCLUSION: CDC2 and CDK2 are activated in HCC, and this may be due to a complex interplay between the level of the cyclin, CDK, CDK inhibitors, and inhibitory phosphorylation.     

Activation of cyclin‐dependent kinases CDC2 and CDK2 in hepatocellular carcinoma

Abstract: Background: The cyclin‐dependent kinases (CDKs) CDC2 and CDK2 are key regulators of the cell cycle. The expression of the CDK alone does not necessary reflect their true activities because they are highly regulated by post‐translational mechanisms. Human hepatocellular carcinoma (HCC) is one of the most common cancers in the world, but the kinase activities of CDKs in HCC have not been examined. Methods: Here we examined the protein expression and kinase activities associated with CDC2 and CDK2 in HCC and the corresponding non‐tumorous liver tissues. Results: CDC2 and CDK2 are activated in HCC in over 70% and 80% of the cases, respectively, but have little correlation with clinical parameters and PCNA expression. Interestingly, PCNA was readily detectable in extracts from non‐tumorous liver, but more than 60% of samples contain higher concentration of PCNA in HCC than the corresponding non‐tumorous tissues. CDC2 and CDK2 are generally activated in the same HCC samples, but the extent of their activation varied significantly, suggesting that the pathways leading to the activation of CDC2 and CDK2 can be regulated independently. Both positive regulators of CDK activity like cyclins and CDKs, and negative regulators of CDK activity like p21^CIP1/WAF1 and Thr14/Tyr15 phosphorylation were up‐regulated in HCC. Conclusion: CDC2 and CDK2 are activated in HCC, and this may be due to a complex interplay between the level of the cyclin, CDK, CDK inhibitors, and inhibitory phosphorylation.     

CyclinD1、CyclinE、CDK6在原发性肝细胞癌中的表达

探讨细胞周期调控因子CyclinD1、CyclinE、CDK6在原发性肝细胞癌中的表达及意义。应用免疫组织化学、原位分子杂交和细胞图象分析技术检测原发性肝细胞癌组织及其对应的癌旁肝组织(各20例)、正常肝组织(5例)中CyclinD1、CyclinE和CDK6mRNA表达情况。结果显示:CyclinD1、CyclinE和CDK6mRNA在肝细胞癌组织中呈阳性表达,阳性率分别为70%、75%和25%,正常肝组织呈阴性表达;肝细胞癌组织中CyclinD1和CyclinE的阳性表达与癌旁肝组织、正常肝组织相比,差异均有显著性意义(P<0.05);CyclinD1和CyclinE的过表达在肝细胞癌的发生和发展中起着重要作用。     

p16,CDK4和Rb在人肝细胞癌中的表达

目的分析ｐ１６基因、细胞周期蛋白依赖性激酶（ＣＤＫ４）和视网膜母细胞瘤基因（Ｒｂ）在人肝细胞癌中表达的改变。方法用免疫组织化学方法对４０例肝细胞癌和癌分组织作检测。结果肝癌组织中的ｐ１６蛋白、ＣＤＫ４和Ｒｂ蛋白的异常表达分别为９４．４４％（３４／３６）、４０．００％（１６／４０）和４５．７１％（１６／３５）。ｐ１６蛋白阴性或弱阳性而ｐＲｂ呈强阳性者１３例（１３／３４,３８．２３％）,两者的表达呈负相关关系二和Ｒｂ均异常者１５例（１５／３４,４４．１１％）,表明Ｒｂ表达的调节除ｐ１６外,还有其他的途径。ＣＤＫ４过度表达的１４例中大多伴Ｐ１６的改变（１３／１４,９２．８５％）,５０．００％能影响Ｒｂ蛋白的表达,同时伴ｐ１６和Ｒｂ异常者为４６．１５％。三者的异常表达与肝癌的恶性程度无相关关系。结论细胞调节因子Ｐ１６基因、ＣＤＫ４和Ｒｂ的表达异常,均参与肝细胞癌的发生。以ｐ１６蛋白表达的改变最为明显。     

Gradual upregulation of OCI-5 expression during occurrence and progression of rat hepatocellular carcinoma

BACKGROUND: OCI-5, the rat homologene of human glypican 3 ( GPC3), is confirmed upregulated in hepatocellular carcinoma (HCC). The present study was undertaken to detect gene expression change of OCI-5 during occurrence and progression of rat HCC. METHODS: Male Sprague-Dawley rats were given diethyl-nitrosamine ( DENA) to induce HCC. Three DENA-induced rats and one control rat were sacrificed every week for 18 weeks during the development of HCC. Tissues specimens were snap-frozen in liquid nitrogen and total RNA was isolated. Sk-Hepl cells were treated with DENA at different concentrations. The gene expression levels of OCI-5 and GPC3 were detected with the RT-PCR method. RESULTS: OCI-5 was not expressed in normal rat liver tissues. When HCC occurred and aggravated, OCI-5 expression was gradually elevated to a very high level. GPC3 was not expressed in the DENA-treated Sk-Hepl cells. CONCLUSIONS: OCI-5 was not expressed in normal rat liver tissues but in rat HCC tissues. High-expression of OCI-5 in DENA-induced rat HCC model was the gene expression change of HCC not the DENA-induced gene expression. The expression level of OCI-5 was not only elevated in rat HCC but also gradually along the occurrence and progression of HCC, indicating that GPC3 might serve as a sensitive marker of early stage HCC.     

Reduced expression of chemokine receptors on peripheral blood lymphocytes in patients with hepatocellular carcinoma

OBJECTIVES: Hepatocellular carcinoma (HCC) is a rapidly progressive malignancy. Chemokine receptors are important mediators of lymphocyte migration in cancer. This study evaluated expression of chemokine receptors on lymphocytes of HCC patients. METHODS: Chemokine receptor expression on peripheral blood lymphocytes (PBL) was determined by flow cytometry and RT-PCR. Tumor infiltrating lymphocytes (TIL) and adjacent nontumor liver infiltrating lymphocytes (NIL) were also studied. RESULTS: The expressions of CCR5, CCR6, and CXCR3 on PBL were significantly reduced in HCC patients compared with normal controls, which occurred concurrently with increased expression of the chemokine receptors in TIL and NIL. Reduced expression of CXCR3 on PBL correlated with large tumor size and advanced tumor stage. The reduced chemokine receptor expression was consistent with the reduced mRNA levels and intracellular protein levels in PBL. HCC patients exhibited lower proportions of CD4(+) and CD8(+) T cells with CCR5, CCR6, and CXCR3 expression on PBL, which occurred concurrently with the increased expression of these chemokine receptors on TIL and NIL. The reduced CCR6 and CXCR3 expression on PBL correlated with the reduced memory phenotype in circulation and increased memory phenotype in liver. Furthermore, CCR5-expressing memory T cells were increased in liver compartment compared with circulation. CONCLUSION: This study demonstrated that reduced chemokine receptor expression on PBL was concurrent with increased chemokine receptor expression on both TIL and NIL in HCC. The results demonstrated the role of chemokine receptors in recruitment of lymphocytes from peripheral blood to HCC. The findings have important implications in understanding of immunopathogenesis of HCC.     

Expression and significance of new inhibitor of apoptosis protein survivin in hepatocellular carcinoma

AM: To investigate expression and significance of inhibitor of apoptosis protein survivin in hepatocellular carcinoma (HCC). METHODS: The expression of survivin and vascular endothelial growth factor (VEGF) was investigated in 38 cases of HCC tissues and 38 liver cirrhosis tissues by immunohistochemistry and Western blot. The relationship between the expression of survivin and clinicopathological factors of HCC was analyzed. RESULTS: Survivin protein was detected in 23 (60.5%) of 38 HCCs and 3 (7.9%) of 38 liver cirrhosis tissues. In 23 cases of HCC which expressed survivin, the expression of VEGF was positive in 18 cases and slight positive or negative in 5 cases. While in 15 cases of HCC which did not express survivin, 12 cases did not express or slightly expressed, and 3 cases expressed VEGF. In liver cirrhosis tissues, the expression of VEGF was as follows: 24 cases were negative, 10 cases were weak positive and 4 cases were strong positive. The expression of survivin was coincident with the expression of VEGF in HCC (P<0.01). The expression of survivin in HCC had no relationship with the patients' age, gender, tumor size and differentiation level of HCC, while it was related to the metastasis of HCC. The protein quantitative analysis by Western blot also showed that overexpression of survivin in HCC was closely correlated to the expression of VEGF (P<0.01). Furthermore, stronger expression of survivin and VEGF was also found in patients with metastasis rather than in those with no metastasis (P<0.01). CONCLUSION: Survivin plays a pivotal role in the metastasis of HCC, and it has some correlation with tumorigenesis. The expression of survivin in the primary lesion is very useful as an indicator for metastasis and prognosis of HCC. It could become a new target of gene therapy of HCC.     

Liver expression of Nrf2-related genes in different liver diseases

BACKGROUND: The KEAP1-Nrf2 antioxidant signaling pathway is important in protecting liver from various insults. However,little is known about the expression of Nrf2-related genes in human liver in different diseases.METHODS: This study utilized normal donor liver tissues(n=35), samples from patients with hepatocellular carcinoma(HCC, n=24), HBV-related cirrhosis(n=27), alcoholic cirrhosis(n=5) and end-stage liver disease(n=13). All of the liver tissues were from the Oriental Liver Transplant Center, Beijing,China. The expressions of Nrf2 and Nrf2-related genes, including its negative regulator Kelch-like ECH-associated protein 1(KEAP1), its targeted gene NAD(P)H-quinone oxidoreductase 1(NQO1), glutamate-cysteine ligase catalytic subunit(GCLC) and modified subunit(GCLM), heme oxygenase 1(HO-1) and peroxiredoxin-1(PRDX1) were evaluated. RESULTS: The expression of Nrf2 was decreased in HCC, increased in alcoholic cirrhosis and end-stage liver disease. The expression of KEAP1 was increased in all of the liver samples.The most notable finding was the increased expression of NQO1 in HCC(18-fold), alcoholic cirrhosis(6-fold), endstage liver disease(5-fold) and HBV-related cirrhosis(3-fold).Peri-HCC also had 4-fold higher NQO1 m RNA as compared to the normal livers. GCLC m RNA levels were lower only in HCC, as compared to the normal livers and peri-HCC tissues.GCLM m RNA levels were higher in HBV-related cirrhosis and end-stage liver disease. HO-1 m RNA levels were increased in all liver tissues except for HCC. Peri-HCC had higher PRDX1 m RNA levels compared with HCC and normal livers.CONCLUSION: Nrf2 and Nrf2-related genes are aberrantly expressed in the liver in different diseases and the increase of NQO1 was the most notable finding, especially in HCC.