Twist ARF和E-cadher in在大肠癌组织中的表达及临床意义

Expression of Twist, ARF and E-cadherin and Its Clinical Significance in Colorectal Cancer

目的:探讨Twist、ARF、E-cadherin蛋白在大肠癌组织中的表达与临床病理参数的关系。同时分析Twist、ARF、E-cadherin与大肠癌生长,侵袭转移之间的关系。方法:采用免疫组织化学SP染色方法对60例大肠癌标本及60例正常大肠黏膜标本分别进行Twist、ARF、E-cadherin蛋白检测。结果:Twist在肿瘤组织中的阳性表达率明显高于正常大肠黏膜(P<0.05);ARF及E-cadherin在肿瘤组织中的阳性表达率明显低于正常大肠黏膜(P<0.05),差异有统计学意义。Twist的表达与大肠癌的病理学分级、肠壁浸润深度、有无淋巴结转移、TNM分期相关(P<0.05)。ARF、E-cadherin的表达与大肠癌的病理学分级、肠壁浸润深度、有无淋巴结转移、TNM分期、有无远处转移相关(P<0.05)。Twist与ARF共同阳性者10例,共同阴性者8例,两者呈显著性负相关(r=0.806,P=0.004)。Twist与E-cadherin共同阳性者3例,共同阴性者7例,两者呈显著性负相关(r=0.754,P=0.006)。结论:Twist的过度表达,ARF、E-cadherin蛋白的表达缺失在大肠癌的发生及侵袭转移中起重要的作用,Twist通过调节ARF/MDM2/p53途径抑制细胞凋亡促进肿瘤细胞形成,同时影响E-cadherin的表达而促进上皮-间质转化现象,参与大肠癌的发生和转移。

Objective： To study the correlation oftbe expression of Twist, ARF and E-cadherin with the clinicopathologie parameters of colorectal cancer, and to analyze the relationships among Twist, ARF and E-cadherin proteins and tumorigenesis, invasion and metastasis of colorectal cancer. Methods： Immunohistochemistry staining （SP） was conducted to detect the expression of Twist, ARF and E-cadherin protein in 60 samples of colorectal tumors and 60 samples of normal colorectal mucosa. Results： The positive rate of Twist was significantly higher in the carcinoma samples than in the normal colorectal mucosa （ P 〈 0.05 ）. The positive rate of ARF and E-cadherin was significantly lower in the carcinoma samples than in the normal colorectal mucosa （ P〈 0.05 ）. The expression of Twist was correlated with the pathological grading of the colorectal cancer, the depth of tumor infiltration into the wall of the large intestine, the presence of lymph node metastases and TNM staging （ P 〈 0.05）. The expression of ARF and E-cadherin was correlated with pathological grade of the cancer, depth of tumor infiltration, the presence of lymph node metastases, TNM stage and the presence of distant metastasis （ P 〈 0.05 ）. There were 10 cases with equally positive expression of Twist and ARF in the colorectal carcinoma group and 8 with equally negative expression. There was a significant negative correlation between Twist and ARF expression in the carcinoma samples （ r = 0.806, P= 0.004 〈 0.05 ）. There were 3 colorectal carcinoma cases with simultaneous positive expression of Twist and E-cadherin and 7 with simultaneous negative expression. There was a remarkable negative correlation between Twist and E-cadberin expression in colorectal carcinoma （ r = 0.754, P = 0.006 〈 0.05）. Conclusion- The overexpression of Twist and underexpression of ARF and E-eadherin may play an important role in the tumorigenesis, invasion and metastasis of colorectal cancer. Twist can inhibit apoptosis and promote tumor cell formation by regulating the ARF/MDM2/P53 pathway. Twist can also simultaneously affect the expression of E-eadherin and promote epithelial mesenchymal transition （EMT）, thus participating in the genesis and metastasis of colorectal cancer.