eIF4E在肾透明细胞癌组织中的表达及意义
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摘要
目的探讨真核细胞翻译起始因子4E(eukaryotic translation initiation factor 4E,eIF4E)在人肾癌组织中的表达及意义。方法采用免疫组织化学法检测40例肾癌组织及40例癌旁组织中eIF4E蛋白的表达。RT-PCR检测eIF4EmRNA在不同临床分期的肾癌组织与癌旁组织中的表达。Western blot法检测不同临床分期的肾癌组织与癌旁组织中eIF4E和Phospho-eIF4E蛋白的表达。结果 eIF4E蛋白在肾癌组织阳性表达率为77.5%,癌旁组织阳性表达率为27.5%,肾癌组织中eIF4E阳性表达率明显高于癌旁组织(P<0.05)。eIF4E mRNA在肾癌中的表达量高于癌旁组织(0.859±0.064 vs.0.705±0.072,P<0.05),且eIF4EmRNA在Ⅲ期肾癌组织中的相对表达量最高(0.961±0.043)。在临床Ⅰ期与Ⅱ期、Ⅰ期与Ⅲ期及Ⅱ期与Ⅲ期肾癌组织间,eIF4E mRNA的表达均有统计学差异(P<0.05)。Western blot法检测发现,肾癌组的eIF4E蛋白和Phospho-eIF4E表达量明显高于癌旁组(分别为:0.676±0.095vs.0.556±0.056;0.605±0.066 vs.0.466±0.045,P<0.05)。在肾癌的不同临床分期中,随着临床分期越高,eIF4E和Phospho-eIF4E蛋白表达量逐渐增高(Ⅰ期:0.629±0.085和0.588±0.058;Ⅱ期:0.699±0.049和0.596±0.061;Ⅲ期:0.812±0.053和0.689±0.046;P<0.05)。Phospho-eIF4E/eIF4E的比值在肾癌组明显高于癌旁组(P<0.05)。但在不同临床分期肾癌之间,Phospho-eIF4E/eIF4E的比值未见统计学差异(P>0.05)。结论eIF4E和PhosphoeIF4E在肾透明细胞癌中高表达,与肾癌的发生、发展有关,为肾癌的诊断及治疗提供了理论依据。
Objective To investigate the expression and role of eukaryotic translation initiation factor 4E(eIF4E)in the tissues of renal cell carcinoma(RCC).Methods eIF4 Eprotein was detected in 40 cases of RCC and40 cases of paraneoplastic renal tissue specimens by immunohistochemistry.eIF4 E mRNA was detected at different clinical stages of RCC specimens by RT-PCR;the expressions of eIF4 Eand Phospho-eIF4 Eprotein were detected by Western blot method.Results There was a significantly higher positive rate(77.5%)of eIF4 Eprotein in RCC than in paraneoplastic renal tissues(27.5%)(P<0.05).The expression of eIF4 E mRNA in RCC was significantly higher than in paraneoplastic renal tissue(0.859±0.064 vs.0.705±0.072,P<0.05).The overexpression of eIF4 EmRNA in RCC was correlated with clinical stage(P <0.05).The expressions of eIF4 Eand Phospho-eIF4 E protein were significantly higher than in paraneoplastic renal tissue(0.676±0.095 vs.0.556±0.056 and 0.605±0.066 vs.0.466±0.045,P <0.05).They were also significantly associated with RCC tumor stages(P<0.05).ConclusionOverexpressions of eIF4 Eand Phospho-eIF4 Eare correlated with the occurrence of RCC,which suggests that the positive expressions of eIF4 Eand Phospho-eIF4 Emay be of some value in diagnosis and therapy of RCC.
Objective To investigate the expression and role of eukaryotic translation initiation factor 4E(eIF4E)in the tissues of renal cell carcinoma(RCC).Methods eIF4 Eprotein was detected in 40 cases of RCC and40 cases of paraneoplastic renal tissue specimens by immunohistochemistry.eIF4 E mRNA was detected at different clinical stages of RCC specimens by RT-PCR;the expressions of eIF4 Eand Phospho-eIF4 Eprotein were detected by Western blot method.Results There was a significantly higher positive rate(77.5%)of eIF4 Eprotein in RCC than in paraneoplastic renal tissues(27.5%)(P<0.05).The expression of eIF4 E mRNA in RCC was significantly higher than in paraneoplastic renal tissue(0.859±0.064 vs.0.705±0.072,P<0.05).The overexpression of eIF4 EmRNA in RCC was correlated with clinical stage(P <0.05).The expressions of eIF4 Eand Phospho-eIF4 E protein were significantly higher than in paraneoplastic renal tissue(0.676±0.095 vs.0.556±0.056 and 0.605±0.066 vs.0.466±0.045,P <0.05).They were also significantly associated with RCC tumor stages(P<0.05).ConclusionOverexpressions of eIF4 Eand Phospho-eIF4 Eare correlated with the occurrence of RCC,which suggests that the positive expressions of eIF4 Eand Phospho-eIF4 Emay be of some value in diagnosis and therapy of RCC.
引文
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[3]KOUVARAKI MA,LIAKOU C,PARASCHI A,et al.Activation of mTOR signaling in medullary and aggressive papillary thyroid carcinomas[J].Surgery,2011,150(6):1258-1265.
[4]SATHEESHA S,COLEMAN LJ,INGRAM N,et al.Response to mTOR inhibition:Activity of eIF4Epredicts sensitivity in cell lines and acquired changes in eIF4Eregulation in breast cancer[J].Mol Cancer,2011,10(1):19.
[5]FURIC L,RONG LW,LARSSON O,et al.eIF4Ephosphorylation promotes tumorigenesis and is associated with prostate cancer progression[J].Proc Natl Acad Sci USA,2010,107(32):14134-14139.
[6]CHEN WQ,ZHENG RS,BAADE PD,et al.Cancer statistics in China,2015[J].CA Cancer J Clin,2016,66(2):115-132.
[7]STEWART GD,MAHONY FC,POWLES T,et al.What can molecular pathology contribute to the management of renal cell carcinoma?[J].Nat RevUrol,2011,8(5):255-265.
[8]NATHAN CO,AMIRGHAHARI N,ABREO FX,et al.Overexpressed eIF4Eis functionally active in surgical margins of head and neck cancer patients via activation of the Akt/mammalian target of rapamycin pathway[J].Clin Cancer Res,2004,10(17):5820-5827.
[9]WANG XL,CAI HP,GE JH,et al.Detection of eukaryotic translation initiation factor 4Eand its clinical significance inhepatocellular carcinoma[J].World J Gastroenterol,2012,18(20):2540-2544.
[10]THOREEN CC,CHANTRANUPONG L,KEYS HR,et al.A unifying model for mTORC1-mediated regulation of mRNA translation[J].Nature,2012,485(7396):109-113.