结直肠癌中CXCR5、CXCL13、MMP-12和MMP-13的表达及意义
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摘要
目的观察结直肠癌组织中趋化因子CXCR5及其配体CXCL13以及MMP-12、MMP-13的表达,探讨其与临床病理特征、预后的关系。方法应用免疫组织化学SP法检测236例结直肠癌及其切缘正常肠黏膜组织以及62例结直肠腺瘤组织中CXCR5、CXCL13、MMP-12和MMP-13蛋白表达。结果 (1)CXCR5、CXCL13、MMP-12、MMP-13在结直肠癌组织中的表达率为43.6%、41.5%、83.5%和80.5%均高于在切缘正常肠黏膜组织中的表达率(4.2%、5.5%、11.9%和13.1%)及在结直肠腺瘤组织中的表达率(24.2%、17.7%、69.4%和64.5%)(P均<0.05)。(2)CXCR5、CXCL13、MMP-12、MMP-13蛋白表达与淋巴结转移、远处转移、肿瘤分期及复发呈正相关(P<0.05)。CXCL13蛋白表达与组织分化程度呈正相关(P<0.05)。(3)CXCR5与CXCL13蛋白表达呈正相关(P<0.05)。CXCR5、CXCL13蛋白表达分别与MMP-12和MMP-13呈正相关(P<0.05)。结论 CXCR5、CXCL13、MMP-12、MMP-13的表达促进结直肠癌的发生、发展以及转移、复发,可作为预测结直肠癌转移和复发的有价值指标。
Objective To investigate the expression of CXCR5, CXCL13, MMP-12 and MMP-13, and to explore their relationship with clinicopathologic features and prognosis of colorectal carcinoma. Methods The immunohistochemistry staining method was used to detect the expression of CXCR5, CXCL13, MMP-12 and MMP-13 protein in 236 paired specimens of colorectal cancer and normal tissues and 62 cases of colorectal adenoma. Results The positive rates of CXCR5, CXCL13, MMP-12 and MMP-13 were 43.6%, 41.5%, 83.5% and 80.5% in colorectal carcinoma tissues, respectively, which were much higher than those in incisal edge normal intestinal mucosa tissues(4.2%, 5.5%, 11.9% and 13.1%) and those in colorectal adenomas tissues(24.2%, 17.7%, 69.4% and 64.5%)(P<0.05). The expression of CXCR5, CXCL13, MMP-12 and MMP-13 were positively correlated with lymph node metastasis, distant metastasis, TNM stage and relapse(P <0.05). Additionally, CXCL13 positive staining was correlated with poor differentiation(P<0.05). CXCR5 expression was significantly correlated with CXCL13 expression(P<0.05). The expression of CXCR5 and CXCL13 were positively correlated with MMP-12 and MMP-13, respectively(P<0.05). Conclusion The expression of CXCR5,CXCL13,MMP-12 and MMP-13 may play a crucial role in the carcinogenesis, development, metastasis and relapse of colorectal cancer. They could be used as prognostic markers of colorectal cancer in clinical practice.
Objective To investigate the expression of CXCR5, CXCL13, MMP-12 and MMP-13, and to explore their relationship with clinicopathologic features and prognosis of colorectal carcinoma. Methods The immunohistochemistry staining method was used to detect the expression of CXCR5, CXCL13, MMP-12 and MMP-13 protein in 236 paired specimens of colorectal cancer and normal tissues and 62 cases of colorectal adenoma. Results The positive rates of CXCR5, CXCL13, MMP-12 and MMP-13 were 43.6%, 41.5%, 83.5% and 80.5% in colorectal carcinoma tissues, respectively, which were much higher than those in incisal edge normal intestinal mucosa tissues(4.2%, 5.5%, 11.9% and 13.1%) and those in colorectal adenomas tissues(24.2%, 17.7%, 69.4% and 64.5%)(P<0.05). The expression of CXCR5, CXCL13, MMP-12 and MMP-13 were positively correlated with lymph node metastasis, distant metastasis, TNM stage and relapse(P <0.05). Additionally, CXCL13 positive staining was correlated with poor differentiation(P<0.05). CXCR5 expression was significantly correlated with CXCL13 expression(P<0.05). The expression of CXCR5 and CXCL13 were positively correlated with MMP-12 and MMP-13, respectively(P<0.05). Conclusion The expression of CXCR5,CXCL13,MMP-12 and MMP-13 may play a crucial role in the carcinogenesis, development, metastasis and relapse of colorectal cancer. They could be used as prognostic markers of colorectal cancer in clinical practice.
引文
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[2]Markowitz SD,Dawson DM,Willis J,et al.Focus on colon cancer[J].Cancer Cell,2002,1(3):233-6.
[3]Labianca R,Nordlinger B,Beretta GD,et al.Primary colon cancer:ESMO Clinical Practice Guidelines for diagnosis,adjuvant treatment and follow-up[J].Ann Oncol,2010,21 Suppl 5:v70-7.
[4]Franciszkiewicz K,Boissonnas A,Boutet M,et al.Role of chemokines and chemokine receptors in shaping the effector phase of the antitumor immune response[J].Cancer Res,2012,72(24):6325-32.
[5]Kataoka H,Tanaka H,Nagaike K,et al.Role of cancer cell-stroma interaction in invasive growth of cancer cells[J].Hum Cell,2003,16(1):1-14.
[6]Müller G,Hopken UE,Lipp M.The impact of CCR7 and CXCR5on lymphoid organ development and systemic immunity[J].Immunol Rev,2003,195:117-35.
[7]Bürkle A,Niedermeier M,Schmitt-Groff A,et al.Overexpression of the CXCR5 chemokine receptor,and its ligand,CXCL13 in B-cell chronic lymphocytic leukemia[J].Blood,2007,110(9):3316-25.
[8]Meijer J,Zeelenberg IS,Sipos B,et al.The CXCR5 chemokine receptor is expressed by carcinoma cells and promotes growth of colon carcinoma in the liver[J].Cancer Res,2006,66(19):9576-82.
[9]Freije JM,Díez-Itza I,Balbín M,et al.Molecular cloning and expression of collagenase-3,anovel human matrix metalloproteinase produced by breast carcinomas[J].J Biol Chem,1994,269(24):16766-73.
[10]Mori M,Barnard GF,Mimori K,et al.Overpression of matri x metalloproteinase-7 m RNA in human colon carcinomas[J].Cancer,1995,75(6 Suppl):1516-9.
[11]VAN Nguyen S,Skarstedt M,Lfgren S,et al.Gene polymorphism of matrix metalloproteinase-12 and-13 and association with colorectal cancer in Swedish patients[J].Anticancer Res,2013,33(8):3247-50.
[12]Razis E,Kalogeras KT,Kotoula V,et al.Improved outcome of high-risk early HER2 positive breast cancer with high CXCL13-CXCR5 messenger RNA expression[J].Clin Breast Cancer,2012,12(3):183-93.
[13]Rath T,Stockle J,Roderfeld M,et al.Matrix metalloproteinase-13 is regulated by toll-like receptor-9 in colorectal cancer cells and mediates cellular migration[J].Oncol Lett,2011,2(3):483-8.