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目的探讨MMP-2、MMP-9和TIMP-2蛋白表达与结直肠癌侵袭转移的关系,寻找用于预测结直肠癌侵袭转移的分子标记物。方法组织微阵列结合免疫组化技术检测结直肠癌及其癌旁正常肠黏膜上皮中的MMP-2、MMP-9和TIMP-2蛋白表达。结果结直肠癌组织中,MMP-9蛋白阳性表达率显著高于癌旁肠黏膜组织(P<0.001),TIMP-2蛋白阳性表达率显著低于癌旁黏膜组织(P<0.05)。浸润至肠壁浆膜层的结直肠癌和Dukes C、D期癌组织的MMP-2蛋白阳性表达率显著高于浸润肠壁浅、深平滑肌层和Dukes A、B期结直肠癌(P<0.05);肠壁局部淋巴结转移的结直肠癌中MMP-2、MMP-9蛋白阳性表达率显著高于无淋巴结转移癌(P<0.05);Dukes A、B期结直肠癌TIMP2蛋白阳性表达率显著高于Dukes C、D期(P<0.05)。TIMP2蛋白阳性的结直肠癌生存时间显著长于TIMP2阴性的结直肠癌(P<0.05)。结直肠癌中MMP-2蛋白阳性表达与MMP-9表达呈正相关(P<0.001),但TIMP-2蛋白阳性表达与MMP-2表达呈显著负相关(P<0.05)。二变量多因素回归分析显示,MMP-2蛋白表达、癌组织的浸润深度和Dukes分期可作为预测结直肠癌淋巴结转移的独立指标。结论结直肠癌MMP-9和TIMP-2蛋白共同高表达及MMP-2与TIMP-2蛋白的表达失衡在结直肠癌侵袭、转移中起重要作用。MMP-2蛋白表达可作为结直肠癌淋巴结转移的独立预测指标。
Objective To investigate the relationship between the expression of MMP-2, MMP-9 and TIMP-2 protein and the invasion and metastasis of colorectal cancer and to find the molecular markers for predicting the invasion and metastasis of colorectal cancer. Methods The expression of MMP-2, MMP-9 and TIMP-2 in colorectal cancer and adjacent normal mucosal epithelium was detected by tissue microarray combined with immunohistochemistry. Results The positive rate of MMP-9 protein in colorectal cancer tissues was significantly higher than that in para-cancerous tissues (P <0.001). The positive rate of TIMP-2 protein in colorectal cancer tissues was significantly lower than that in para-cancerous mucosa tissues (P <0.05). The positive rates of MMP-2 protein in colorectal cancer and Dukes C and D tissues infiltrating into the intestinal wall serosa were significantly higher than those in the infiltrating intestinal wall, deep smooth muscle layer and Dukes A and B colorectal cancer (P < 0.05). The positive rates of MMP-2 and MMP-9 in colorectal cancer with colorectal wall lymph node metastasis were significantly higher than those without lymph node metastasis (P <0.05). The positive rates of TIMP2 protein expression in Dukes A and B colorectal cancer Significantly higher than Dukes C, D (P <0.05). The survival time of TIMP2-positive colorectal cancer was significantly longer than that of TIMP2-negative colorectal cancer (P <0.05). The positive expression of MMP-2 in colorectal cancer was positively correlated with the expression of MMP-9 (P <0.001), but negatively correlated with the expression of TIMP-2 protein and MMP-2 (P <0.05). Two-variable multivariate regression analysis showed that MMP-2 protein expression, depth of invasion and Dukes staging of cancerous tissue could be used as independent predictors of lymph node metastasis in colorectal cancer. Conclusion The overexpression of MMP-9 and TIMP-2 in colorectal cancer and the imbalance of MMP-2 and TIMP-2 expression play an important role in the invasion and metastasis of colorectal cancer. MMP-2 protein expression can be used as an independent predictor of lymph node metastasis of colorectal cancer.