结肠直肠癌Smad4、MMP-9基因表达的相关研究

目的研究结肠直肠癌组织中Smad4、MMP-9的表达与血管生成、侵袭转移之间的关系，探讨Smad4和MMP-9之间的相关性。方法采用Max Vision快捷免疫组化法，对47例人结肠直肠癌组织和23例癌旁正常组织做Smad4、MMP-9、CD34的抗原标记，并以CD34标记血管内皮细胞，计数微血管密度（MVD）。结果结肠直肠癌组织中的Smad4阳性率（46，81％）明显低于癌旁正常组织（86．96％），MMP-9的阳性率（57．45％）明显高于癌旁正常组织（17．39％）；Smad4表达阳性的结肠直肠癌组织MVD值（24．95±4．53）明显低于表达阴性者（31．22±6．39），MMP-9表达阳性的结肠直肠癌组织MVD值（30．52±7．08）明显高于表达阴性者（25．25±3．63）；Smad4、MMP-9的表达及MVD与结肠直肠癌的组织学分级、淋巴结转移、Duke’s分期密切相关，而与性别、年龄和肿瘤的部位无关；Smad4、MMP-9在结肠直肠癌中的表达呈负相关。结论Smad4、MMP-9的表达及MVD值与结肠直肠癌的侵袭转移密切相关，可作为重要的生物学标志；MMP-9可能是抑癌基因Smad4调控的下游目的基因。

Expression of Smad4 and MMP-9 genes in colorectal carcinoma

Objective To study the correlation between the expressions of Smad4 and MMP-9 in colorectal carcinoma and the vascularization and biological behaviors and to evaluate the relationship between Smad4 and MMP-9.Methods The expressions of Smad4,MMP-9 and CD34 in 47 cases of carcinoma and 23 cases of peri-neoplasm tissue were detected by shortcut immunohistochemical Max Vision method,and vascular endothelial cell was marked by CD34.Microvessel density(MVD) was calculated.Results The expression of Smad4 was significantly lower in colorectal carcinoma (46.81%) than that in peri-neoplasm tissue(86.96%) and the expression of MMP-9 was significantly higher in colorectal carcinoma(57.45%) than that in peri-neoplasm tissue(17.39%).The MVD in Smad4 positive group(24.95±4.53) was significantly lower than that in Smad 4 negative group(31.22±6.39) and the MVD in MMP-9 positive group (30.52±7.08) was significantly lower than that in MMP-9 negative group(25.25±3.63).The expression levels of Smad4 and MMP-9 and MVD was significantly correlated with histological grades and lymph nodesmetastasis and Dukes stage(P<0.01 or P<0.05),but not with gender,age,and location of tumor.A negative correlation was observed between the expression of Smad4 and that of MMP-9(r=-0.659,P<0.01).Conclusion The expressions of Smad4 and MMP-9 and MVD significantly correlated with biological behaviors of colorectal carcinoma,and therefore may be used as biologic markers.MMP-9 may be a downstream target genes regulated by Smad4.