Twist1和血管生成拟态在结直肠癌中的表达和临床意义

Expression and clinical significance of Twist1 and angiogenesis mimicry in colorectal cancer

目的分析Twist1在结直肠癌(CRC)中的表达及对血管生成拟态(VM)的影响。方法收集124例CRC病例资料,通过免疫组织化学分析CRC组织及正常结直肠黏膜组织中Twist1、血管内皮细胞钙黏连蛋白(VE-cadherin)表达差异及其与预后及临床参数间的关系,对比CRC组织及正常结直肠黏膜组织中存在的VM现象。沉默CRC细胞株Twist1表达水平,通过蛋白免疫印(Western blot)迹检测VM法相关分子表达情况,观察Twist1对于结直肠癌细胞侵袭、迁移和VM的影响。结果与正常结直肠黏膜组织比较,CRC组织Twist1、VE-cadherin阳性率升高,差异有统计学意义(P<0.05)。Twist1、VE-cadherin及VM与CRC的血管侵犯和淋巴结转移有关(P<0.05);总生存率统计分析显示,Twist1高表达CRC患者5年生存率明显低于Twist1低表达患者(P<0.01)。沉默Twist1表达后,si-Twist1组CRC细胞的侵袭、迁移能力较si-NC组(阴性对照)明显降低(P<0.05),上皮间质转化(EMT)相关因子Snail、N-cadherin及VM相关蛋白VE-cadherin的表达水平均较si-NC组明显降低(P<0.05)。结论Twist1在CRC组织中高表达并与肿瘤VM相关,对CRC细胞侵袭、迁移等恶性生物学行为具有重要影响,对评估患者预后具有一定的价值。

Objective To analyze the expression of Twist1 in colorectal cancer(CRC)and its influence on vasculogenic mimicry(VM).Methods The data of 124 cases of CRC were collected,and the expression levels of Twist1,VE-cadherin in the CRC tissue and normal colorectal mucosal tissues were detected by using the immunohistochemistry,their influence on the prognosis and their relationship with clinical parameters were analyzed.The VM phenomenon was compared between the CRC tissue and normal colorectal mucosal tissue.The expression level of Twist1 was silenced,and the expression levels of VM-related molecules were detected by Western blot.The effect of Twist1 on the invasion,metastasis and VM of CRC was observed.Results Compared with normal colorectal mucosal tissues,the Twist1 and VE-cadherin expression levels in the CRC tissue were increased,the differences were statistically significant(P<0.05).Twist1,VE-cadherin and VM were related to the vascular invasion and lymph node metastasis in colorectum(P<0.05).In the total survival rate statistical analysis,the higher the expression of Twist1,the poorer the prognosis of patients.After silencing the expression level of Twist1,the invasion and migration abilities of CRC cells in the si-Twist1 group group were significantly decreased when compared with the si-NC group(negative group,P<0.05),the expression levels of epithelial-mesenchymal transition(EMT)related factors Snail,Slug and VM related protein VE-cadherin were significantly decreased when compared with the si-NC group(P<0.05).Conclusion Twist1 is highly expressed in CRC tissues and is related to tumor metastasis and VM,which has an important effect on the invasion and metastasis malignant biological behavior and has a certain value on the prognosis evaluation.