结直肠癌组织中FOXO3a与MMP-9的表达及意义
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摘要
目的探讨转录因子叉头框蛋白O3a(FOXO3a)与基质金属蛋白酶9(MMP-9)在结直肠癌组织中的表达以及二者的关系。方法应用组织芯片和免疫组织化学SP法检测FOXO3a与MMP-9在78例结直肠癌组织和69例相应正常肠黏膜组织中的表达,分析FOXO3a和MMP-9蛋白表达与结直肠癌患者临床病理特征的关系及FOXO3a和MMP-9的关系。结果 (1)78例结直肠癌组织与69例正常肠黏膜组织中,FOXO3a的阳性表达率分别为57.69%(45/78)和95.65%(66/69),MMP-9的阳性表达率分别为85.90%(67/78)和15.94%(11/69),FOXO3a与MMP-9在结直肠癌组织和正常肠黏膜组织中表达的差异均具有统计学意义(P=0.000)。(2)结直肠癌组织中FOXO3a低表达、MMP-9过表达与肿瘤浸润深度、分化程度、淋巴结转移和TNM分期密切相关(P<0.05),与患者年龄、性别、肿瘤大小均无关(P>0.05)。(3)FOXO3a的表达与MMP-9的表达呈负相关(r=-0.272,P<0.05)。结论 FOXO3a表达降低及MMP-9表达增高可能与结直肠癌的进展有密切关系,联合检测FOXO3a与MMP-9的表达水平可能对预测结直肠癌的恶性程度和预后有重要意义。
Objective To investigate the expression of FOXO3aand MMP 9in colorectal cancer tissues and their relationship.Methods Tissue microarray and immunohistochemical SP methods were used to detect the expression of FOXO3aand MMP 9in 78cases of colorectal cancer tissues and 69cases of corresponding normal intestinal mucosa tissues,then analyze the relation between their expression and the clinicopathologic parameters of the patients,and the relation between the expression of FOXO3aand MMP 9.Results(1)The positive expression rate of FOXO3ain 78cases of colorectal cancer tissues and 69cases of normal intestinal mucosa tissues are 57.69%(45/78)and 95.65%(66/69),the positive expression rate of MMP 9in 78cases of colorectal cancer tissues and 69cases of normal intestinal mucosa tissues are 85.90%(67/78)and 15.94%(11/69),and the difference is significant(P=0.000).(2)The decreased expression of FOXO3aand the increased expression of MMP 9in colorectal cancer are significantly correlated with the depth of tumor invasion,tumor histological differentiation,metastasis of lymph node and TNM stage(P< 0.05),but there is no significant relationship with patients′age,gender and tumor size(P>0.05).(3)There was a negative correlation between the expression of FOXO3aand MMP 9(r=0.272,P<0.05).Conclusion The decreased expression of FOXO3aand the increased expression of MMP 9may be closely related with carcinogenesis,invasion and metastasis of colorectal cancer,and their combination may be an important indicator to evaluate the malignant degree and prognosis of the colorectal cancer.
Objective To investigate the expression of FOXO3aand MMP 9in colorectal cancer tissues and their relationship.Methods Tissue microarray and immunohistochemical SP methods were used to detect the expression of FOXO3aand MMP 9in 78cases of colorectal cancer tissues and 69cases of corresponding normal intestinal mucosa tissues,then analyze the relation between their expression and the clinicopathologic parameters of the patients,and the relation between the expression of FOXO3aand MMP 9.Results(1)The positive expression rate of FOXO3ain 78cases of colorectal cancer tissues and 69cases of normal intestinal mucosa tissues are 57.69%(45/78)and 95.65%(66/69),the positive expression rate of MMP 9in 78cases of colorectal cancer tissues and 69cases of normal intestinal mucosa tissues are 85.90%(67/78)and 15.94%(11/69),and the difference is significant(P=0.000).(2)The decreased expression of FOXO3aand the increased expression of MMP 9in colorectal cancer are significantly correlated with the depth of tumor invasion,tumor histological differentiation,metastasis of lymph node and TNM stage(P< 0.05),but there is no significant relationship with patients′age,gender and tumor size(P>0.05).(3)There was a negative correlation between the expression of FOXO3aand MMP 9(r=0.272,P<0.05).Conclusion The decreased expression of FOXO3aand the increased expression of MMP 9may be closely related with carcinogenesis,invasion and metastasis of colorectal cancer,and their combination may be an important indicator to evaluate the malignant degree and prognosis of the colorectal cancer.
引文
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[14]Storz P,Dppler H,Copland JA,et al.FOXO3aPromotes Tumor Cell Invasion through the Induction of Matrix Metalloproteinases[J].Mol Cell Biol,2009,29(18):4906-4917.
[15]Ganapathy S,Chen Q,Singh KP,et al.Resveratrol enhances antitumor activity of TRAIL in prostate cancer xenografts through activation of FOXO transcription factor[J].PLoS One,2010,5(12):e15627.
[16]Miyazono K.Tumour promoting functions of TGF-βin CML-initiating cells[J].J Biochem,2012,152(5):383-385.
[2]Coomber BL,Yu JL,Fathers KE,et al.Angiogenesis and the role of epigenetics in metastasis[J].Clin Exp Metastasis,2003,20(3):215-227.
[3]Bendardaf R,Buhmeida A,Hilska M,et al.MMP-9(gelatinase B)expression is associated with disease-free survival and disease-specific survival in colorectal cancer patients[J].Cancer Invest,2010,28(1):38-43.
[4]Chen X,Su Y,Fingleton B,et al.Increased plasma MMP9in integrin alpha1-null mice enhances lung metastasis of colon carcinoma cells[J].Int J Cancer,2005,116(1):52-61.
[5]李学斌,谢庄,石放雄.FOXO蛋白在动物细胞的分化、增殖、免疫、衰老调节中的作用[J].中国临床康复,2006,9(10):158-162.
[6]Hong ZY,Lee HJ,Shin DY,et al.Inhibition of Akt/FOXO3a signaling by constitutively active FOXO3a suppresses growth of follicular thyroid cancer cell lines[J].Cancer Lett,2012,314(1):34-40.
[7]Lu M,Zhao Y,Xu F,et al.The expression and prognosis of FOXO3aand Skp2in human ovarian cancer[J].Med Oncol,2012,29(5):3409-3415.
[8]Zou Y,Tsai WB.Forkhead box transcription factor FOXO3asuppresses estrogen dependent breast cancer cell proliferation and tumorigenesis[J].Breast Cancer Res,2008,10(1):R21.
[9]Shiota M,Song Y,Yokomizo A,et al.FOXO3aSuppression of Urothelial Cancer Invasiveness Regulation through Twist1,Y-Box-Binding Protein 1,and E-Cadherin[J].Clin Cancer Res,2010,16(23):5654-5663.
[10]Quaranta M,Daniele A,Coviello M,et al.MMP-2,MMP-9,VEGF and CA 15.3in breast cancer[J].Anticancer Res,2007,27(5):3593-3600.
[11]Sillanpaa S,Anttila M,Voutilainen K,et al.Prognostic significance of matrix metalloproteinase-9(MMP-9)in epithelial ovarian cancer[J].Gynecol Oncol,2007,104(2):296-303.
[12]Kim SM,Lee H,Park YS,et al.ERK5regulates invasiveness of osteosarcoma by inducing MMP-9[J].J Orthop Res,2012,30(7):1040-1044.
[13]Chiang AC,Massague J.Molecular basis of metastasis[J].N Engl J Med,2008,359(26):2814-2823.
[14]Storz P,Dppler H,Copland JA,et al.FOXO3aPromotes Tumor Cell Invasion through the Induction of Matrix Metalloproteinases[J].Mol Cell Biol,2009,29(18):4906-4917.
[15]Ganapathy S,Chen Q,Singh KP,et al.Resveratrol enhances antitumor activity of TRAIL in prostate cancer xenografts through activation of FOXO transcription factor[J].PLoS One,2010,5(12):e15627.
[16]Miyazono K.Tumour promoting functions of TGF-βin CML-initiating cells[J].J Biochem,2012,152(5):383-385.