结肠癌组织中趋化因子受体CXCR4、基质金属蛋白酶-9的表达及其意义

Expression of chemokine receptor CXCR4 and matrix metalloproteinase-9 in human colorectal carcinoma and its significance

目的观察趋化因子受体CXCR4及基质金属蛋白酶(MMP)-9在结肠癌组织中的表达及其临床意义,探讨其与结肠癌的侵袭转移及预后的关系。方法采用免疫组织化学方法检测74例患者的结肠癌组织及癌旁正常黏膜组织中CXCR4、MMP-9的表达及分布,并分析CXCR4及MMP-9与结肠癌淋巴结转移之间的关系。采用逆转录-聚合酶链反应检测30例结肠癌组织及正常黏膜组织的CXCR4表达,并分析不同表达程度与淋巴结转移之间的关系。结果CXCR4表达于细胞膜和细胞质,呈淡黄至棕黄色,细胞核不染色。结肠癌组织CXCR4阳性表达率为54.1%(40/74),显著高于癌旁正常黏膜组织的33.8%(25/74,P<0.05)。有淋巴结转移患者结肠癌组织标本的CXCR4阳性表达率为73.5%(25/34),显著高于无淋巴结转移者的37.5% (15/40,P<0.01)。癌组织中CXCR4 mRNA的表达量明显高于癌旁正常黏膜组织;癌组织CXCR4与β-actin的灰度值比为1.053±0.097,显著高于癌旁正常黏膜组织的0.807±0.095(P<0.01)。结肠癌组织标本MMP-9阳性表达率为59.5%(44/74)。有淋巴结转移患者结肠癌组织标本的MMP-9阳性表达率为82.4% (28/34),显著高于无淋巴结转移者的40.0%(16/40,P<0.01)。CXCR4与MMP-9在结肠癌中存在相关性(k=0.564,P<0。01)。结论CXCR4、MMP-9可能与结肠癌的淋巴结转移有关,且两者在结肠癌淋巴结转移过程中可能存在某种调控或协同作用,联合检测CXCR4、MMP-9可预测淋巴结转移及结肠癌预后。

Objective To observe the expression of chemokine receptor CXCR4 and matrix metalloproteinase-9 （MMP-9） in human colorectal carcinoma and its clinical significance, so as to assess their expression with the metastasis and prognosis of colorectal carcinoma. Methods Immunohistochemistry was used to detect the expression of the CXCR4 and MMP-9 in 74 patients with colon cancer. The relationship between the CXCR4 and MMP-9 expression and the clinic pathological characters was statistically analyzed. RT-PCR was used to detect the CXCR4 mRNA expression in the colon cancer tissues and normal mucus in 30 patients. The relationship between expression of CXCR4 with lymphatic metastatsis was analyzed. Results CXCR4 expression was located on the membrane and cytoplasm （light yellow to brown） but not in the nuclei. The positive rate of CXCR4 was 54.1% （40/74） in the cancer tissues, significantly higher than that in the adjacent normal tissue （33.8%, 25/74, P〈0.05）. The positive rate of CXCR4 was 73.5% （25/34） in patients with lymphatic metastasis, which was significantly higher than that without lymphatic metastasis （37.5%, 15/40, P〈0.01）. The expression of CXCR4 mRNA in the cancer tissues was obviously higher the adjacent normal tissue. The grayscale value of CXCR4 to β-actin was 1.053±0.097, which was significantly higher than that of the adjacent normal tissues （0.807±0.095, P〈0.01）. MMP-9 was positive in 59.5%（44/74） of the colon cancer tissues, and 82.4%（28/34）patients with lymphatic metastasis were positive of MMP-9, being significantly higher than those without lymphatic metastasis （40.0%, 16/40, P〈0.01）. The positive rate of CXCR4 was correlated with MMP 9 in colon cancer tissues（κ=0.564,P〈0.01）. Conclusion Expression of CXCR4 and MMP-9 might be associated with lymphatic metastasis;CXCR4 and MMP-9 may work synergistically in the lymphatic metastasis of colon cancer. Detection of CXCR4 and MMP-9 may predict the lymphatic metastasis and prognosis of colon cancer.