Pyk2、Twist及MMP-7在肝细胞癌中的表达及临床意义
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摘要
目的:检测肝癌组织中富含脯氨酸的酪氨酸蛋白激酶2(proline-rich tyrosine kinase-2,Pyk2)、Twist和基质金属蛋白酶-7(MMP-7)的表达,并分析它们相互之间的关系及其临床意义。方法:应用免疫组织化学法检测80例肝癌组织及癌旁肝组织中Pyk2、Twist及MMP-7蛋白的表达情况,分析其与临床病理因素的关系。结果:Pyk2在肝癌组织及癌旁肝组织中的阳性表达率分别为71.3%、12.0%,差异有统计学意义(P<0.05);Twist在肝癌组织及癌旁肝组织中的阳性表达率分别为66.3%、6.0%,差异有统计学意义(P<0.05);MMP-7在肝癌组织及癌旁肝组织中的阳性表达率分别为68.8%、8.0%,差异有统计学意义(P<0.05)。Pyk2阳性表达与肝癌病理分级、分化程度、血管侵犯及TNM分期明显相关(P<0.05),Twist阳性表达与肝癌病理分级、分化程度、血管侵犯及TNM分期明显相关(P<0.05),MMP-7阳性表达与肝癌病理分级、分化程度、血管侵犯及TNM分期明显相关(P<0.05)。肝癌组织中,Pyk2与Twist表达呈正相关(P<0.05),Pyk2和MMP-7表达亦呈正相关(P<0.05),Twist和MMP-7表达亦呈正相关(P<0.05)。结论:Pyk2、Twist和MMP-7蛋白的表达水平在肝癌组织中与肿瘤组织的分化程度、病理分级、血管侵犯及临床TNM分期等均有关。因此,临床联合检测Pyk2、Twist和MMP-7对肝癌患者的预后判断具有重要意义。
Objective:To study the expressions and their clinical significance of Pyk2,Twist and MMP-7 in hepatocellular carcinoma.Method:The expressions of Pyk2,Twist and MMP-7 proteins were tested by immunohistochemistry in 80 cases of hepatocellular carcinomas and adjacent paracancerous tissues.Result:The positive rate of Pyk2 in hepatocellular carcinomas was significantly higher than that of adjacent paracancerous tissues(71.3% vs 12.0%,P<0.05).Significant differences were also observed in the expression rate of Twist between the patients with hepatocellular carcinomas and paracancerous tissues(66.3% vs 6.0%,P<0.05).The positive rate of MMP-7 in hepatocellular carcinomas was significantly higher than that of adjacent paracancerous tissues(68.8% vs 8.0%,P<0.05).The differences of the expression of Pyk2 in hepatocellular carcinoma of pathological grading,tumor differentiation,vascular invasion and clinical TNM stage were significant(P<0.05).The differences of the expression of Twist in hepatocellular carcinoma of pathological grading,differentiation,vascular invasion and clinical TNM stage were also significant(P<0.05).The differences of the expression of MMP-7 in hepatocellular carcinoma of pathological grading,differentiation,vascular invasion and clinical TNM stage were also significant(P<0.05).Significantly positive correlation was found between Pyk2 and Twist by using spearman correlation analysis(P<0.05).There was positive correlation between Pyk2 and MMP-7(P<0.05).There was positive correlation between Twist and MMP-7(P<0.05).Conclusion:The expressions of Pyk2,Twist and MMP-7 are related to the pathological grading,differentiation,vascular invasion and clinical TNM stage,and their combined detection can help estimate the outcomes of the patients.
Objective:To study the expressions and their clinical significance of Pyk2,Twist and MMP-7 in hepatocellular carcinoma.Method:The expressions of Pyk2,Twist and MMP-7 proteins were tested by immunohistochemistry in 80 cases of hepatocellular carcinomas and adjacent paracancerous tissues.Result:The positive rate of Pyk2 in hepatocellular carcinomas was significantly higher than that of adjacent paracancerous tissues(71.3% vs 12.0%,P<0.05).Significant differences were also observed in the expression rate of Twist between the patients with hepatocellular carcinomas and paracancerous tissues(66.3% vs 6.0%,P<0.05).The positive rate of MMP-7 in hepatocellular carcinomas was significantly higher than that of adjacent paracancerous tissues(68.8% vs 8.0%,P<0.05).The differences of the expression of Pyk2 in hepatocellular carcinoma of pathological grading,tumor differentiation,vascular invasion and clinical TNM stage were significant(P<0.05).The differences of the expression of Twist in hepatocellular carcinoma of pathological grading,differentiation,vascular invasion and clinical TNM stage were also significant(P<0.05).The differences of the expression of MMP-7 in hepatocellular carcinoma of pathological grading,differentiation,vascular invasion and clinical TNM stage were also significant(P<0.05).Significantly positive correlation was found between Pyk2 and Twist by using spearman correlation analysis(P<0.05).There was positive correlation between Pyk2 and MMP-7(P<0.05).There was positive correlation between Twist and MMP-7(P<0.05).Conclusion:The expressions of Pyk2,Twist and MMP-7 are related to the pathological grading,differentiation,vascular invasion and clinical TNM stage,and their combined detection can help estimate the outcomes of the patients.
引文
[1]Hsieh C H,Wei C K,Yin W V,et al.Vascular invasion affects survival in early hepatocellular carcinoma[J].Molecular Clinical Oncology,2015,3(1):252-256.
[2]Lim S T,Miller N L,Nam J O,et al.Pyk2 inhibition of p53 as an adaptive and intrinsic mechanism facilitating cell proliferation and survival[J].J Biol Chem,2010,285(3):1743-1753.
[3]Gutenberg A,Bruck W,Buchfelder M,et al.Expression of tyrosine kinases FAK and Pyk2 in 331 human astrocytomas[J].Acta Neuropathol,2004,108(3):224-230.
[4]Zhang S,Qiu X,Gu Y,et al.Up-regulation of proline-rich tyrosine kinase 2 in non-small cell lung cancer[J].Lung Cancer,2008,62(3):295-301.
[5]Marco Genua,Shi-Qiong Xu,Simone Buraschi,et al.ProlineRich Tyrosine Kinase 2(Pyk2)Regulates IGF-I-Induced Cell Motility and Invasion of Urothelial Carcinoma Cells[J].PLo S One,2012,7(6):e40 148.
[6]平金良,顾栋桦,徐炜,等.喉鳞状细胞癌组织Twist表达与上皮-间质转化相关性分析[J].中华肿瘤防治杂志,2015,22(18):1451-1455.
[7]Gao F,Zhang Y,Yang F,et al.Survivin promotes the invasion of human colon carcinoma cells by regulating the expression of MMP7[J].Mol Med Rep,2014,9(3):825-830.
[8]Kimberly D.Fisher,Juan Codina,Snezana Petrovic,et al.Pyk2 regulates H+-ATPase-mediated proton secretion in the outer medullary collecting duct via an ERK1/2 signaling pathway[J].Am J Physiol Renal Physiol,2012,303(9):F1353-F1362.
[9]Selitrennik M,Lev S.PYK2 integrates growth factor and cytokine receptors signaling and potentiates breast cancerinvasion via a positive feedback loop[J].Oncotarget,2015,6(26):22 214-22 226.
[10]Cao J,Chen Y,Fu J,et al.High Expression of Proline-Rich Tyrosine Kinase2 is associated with poor survival of hepatocellular carcinoma via regulating phosphatidylinositol 3-Kinase/AKT pathway[J].Ann Surg Oncol,2012,20(Suppl 3):S312-323.
[11]Verma N,Keinan O,Selitrennik M,et al.PYK2 sustains endosomal-derived receptor signalling and enhances epithelialto-mesenchymal transition[J].Nature Communications,2015,4(6):6064.
[12]杨丞,饶翔,张弦,等.Twist基因转染对人宫颈癌细胞生物学行为影响的观察[J].中华肿瘤防治杂志,2013,20(3):185-190.
[13]张同军,薛栋,刘敏,等.转录因子Twist在胰腺癌中的表达及在上皮间质转化中的作用[J].国际外科学杂志,2014,41(6):382-386.
[14]王琳.Twist蛋白在结直肠癌中的表达水平及其促进癌症发展的机制研究[J].中国现代医学杂志,2016,26(8):28-32.
[15]车娜,赵秀兰,古强,等.Twist、E-cadherin和β-catenin在肝细胞肝癌中的表达及其与预后的关系[J].中国肿瘤临床,2010,37(6):305-308.
[16]Ahmed Haji Omar A,Haglund C,Virolainen S,et al.MMP-7,MMP-8,and MMP-9 in oral and cutaneous squamous cell carcinomas[J].Oral Surg Oral Med Oral Pathol Oral Radiol,2015,119(4):459-467.
[17]Long Z W,Wang J L,Wang Y N.Matrix metalloproteinase-7m RNA and protein expression in gastric carcinoma:a metaanalysis[J].Tumour Biol,2014,35(11):11 415-11 426.
[18]Xiao X Y,Lang X P.Correlation Between MMP-7 and b FGF Expressions in Non-small Cell Lung Cancer Tissue and Clinicopathologic Features[J].Cell Biochem Biophys,2015,73(2):427-432.
[19]Miao S,Zhou S Y,Han C S,et al.Clinicopathological significance of matrix metalloproteinase-7 protein expression in esophageal cancer:a meta-analysis[J].Drug Des Devel Ther,2015,9:3729-3740.
[20]苏书娟.MMP-7和ColⅣ在乳腺导管癌中的表达及其相关性[J].中国医学创新,2012,9(35):1-2.
[2]Lim S T,Miller N L,Nam J O,et al.Pyk2 inhibition of p53 as an adaptive and intrinsic mechanism facilitating cell proliferation and survival[J].J Biol Chem,2010,285(3):1743-1753.
[3]Gutenberg A,Bruck W,Buchfelder M,et al.Expression of tyrosine kinases FAK and Pyk2 in 331 human astrocytomas[J].Acta Neuropathol,2004,108(3):224-230.
[4]Zhang S,Qiu X,Gu Y,et al.Up-regulation of proline-rich tyrosine kinase 2 in non-small cell lung cancer[J].Lung Cancer,2008,62(3):295-301.
[5]Marco Genua,Shi-Qiong Xu,Simone Buraschi,et al.ProlineRich Tyrosine Kinase 2(Pyk2)Regulates IGF-I-Induced Cell Motility and Invasion of Urothelial Carcinoma Cells[J].PLo S One,2012,7(6):e40 148.
[6]平金良,顾栋桦,徐炜,等.喉鳞状细胞癌组织Twist表达与上皮-间质转化相关性分析[J].中华肿瘤防治杂志,2015,22(18):1451-1455.
[7]Gao F,Zhang Y,Yang F,et al.Survivin promotes the invasion of human colon carcinoma cells by regulating the expression of MMP7[J].Mol Med Rep,2014,9(3):825-830.
[8]Kimberly D.Fisher,Juan Codina,Snezana Petrovic,et al.Pyk2 regulates H+-ATPase-mediated proton secretion in the outer medullary collecting duct via an ERK1/2 signaling pathway[J].Am J Physiol Renal Physiol,2012,303(9):F1353-F1362.
[9]Selitrennik M,Lev S.PYK2 integrates growth factor and cytokine receptors signaling and potentiates breast cancerinvasion via a positive feedback loop[J].Oncotarget,2015,6(26):22 214-22 226.
[10]Cao J,Chen Y,Fu J,et al.High Expression of Proline-Rich Tyrosine Kinase2 is associated with poor survival of hepatocellular carcinoma via regulating phosphatidylinositol 3-Kinase/AKT pathway[J].Ann Surg Oncol,2012,20(Suppl 3):S312-323.
[11]Verma N,Keinan O,Selitrennik M,et al.PYK2 sustains endosomal-derived receptor signalling and enhances epithelialto-mesenchymal transition[J].Nature Communications,2015,4(6):6064.
[12]杨丞,饶翔,张弦,等.Twist基因转染对人宫颈癌细胞生物学行为影响的观察[J].中华肿瘤防治杂志,2013,20(3):185-190.
[13]张同军,薛栋,刘敏,等.转录因子Twist在胰腺癌中的表达及在上皮间质转化中的作用[J].国际外科学杂志,2014,41(6):382-386.
[14]王琳.Twist蛋白在结直肠癌中的表达水平及其促进癌症发展的机制研究[J].中国现代医学杂志,2016,26(8):28-32.
[15]车娜,赵秀兰,古强,等.Twist、E-cadherin和β-catenin在肝细胞肝癌中的表达及其与预后的关系[J].中国肿瘤临床,2010,37(6):305-308.
[16]Ahmed Haji Omar A,Haglund C,Virolainen S,et al.MMP-7,MMP-8,and MMP-9 in oral and cutaneous squamous cell carcinomas[J].Oral Surg Oral Med Oral Pathol Oral Radiol,2015,119(4):459-467.
[17]Long Z W,Wang J L,Wang Y N.Matrix metalloproteinase-7m RNA and protein expression in gastric carcinoma:a metaanalysis[J].Tumour Biol,2014,35(11):11 415-11 426.
[18]Xiao X Y,Lang X P.Correlation Between MMP-7 and b FGF Expressions in Non-small Cell Lung Cancer Tissue and Clinicopathologic Features[J].Cell Biochem Biophys,2015,73(2):427-432.
[19]Miao S,Zhou S Y,Han C S,et al.Clinicopathological significance of matrix metalloproteinase-7 protein expression in esophageal cancer:a meta-analysis[J].Drug Des Devel Ther,2015,9:3729-3740.
[20]苏书娟.MMP-7和ColⅣ在乳腺导管癌中的表达及其相关性[J].中国医学创新,2012,9(35):1-2.