大肠腺癌中p27^(kip1)、skp2和p53基因的表达及意义

Expression of p27^(kip1),skp2,p53 gene in colorectal adenocarcinoma and its significance

目的:检测大肠腺癌组织中p27kip1、skp2、p53基因的表达情况,并分析与临床病理参数之间的关系,探讨其与大肠癌发生、发展的关系。方法:应用RT-PCR技术检测60例大肠腺癌、20例正常大肠粘膜组织中p27kip1、skp2、p53mRNA的表达水平,免疫组化SP法检测60例大肠腺癌、20例大肠腺瘤、20例正常大肠粘膜组织中p27kip1、skp2、p53蛋白的表达情况。结果:大肠腺癌组织中p27kip1、skp2、p53mRNA的表达水平分别为0.540±0.155,0.597±0.125,0.302±0.127均与正常大肠粘膜组织有差异(P<0.01)。60例腺癌中p27kip1、skp2、p53的阳性表达与它们在腺瘤和正常粘膜组织中的阳性表达有显著差异(P<0.001)。p53的表达与大肠癌浸润、淋巴转移及Dukes’分期有相关性(P<0.05);p27kip1和skp2的表达与肿瘤细胞分化程度、肿瘤组织浸润深度、Dukes’分期的进展及淋巴结转移有相关性(P<0.05)。p27kip1表达与skp2表达呈负相关(r=-0.714,P<0.001),p53表达与p27kip1表达呈负相关(r=-0.653,P<0.001),而与skp2表达呈正相关(r=0.617,P<0.001)。结论:在大肠癌恶变进程中,p27kip1、skp2和p53表达发生相应变化,它们均可能参与了大肠癌发生、发展的过程,3种基因的联合检测可为临床判断大肠腺癌的恶性生物学行为提供重要参考。

Objective ：To investigate the expression of p27^kip1, skp2 and p53 in colorectal carcinoma. Methods ：The expression of p27^kip1, skp2, p53 gene mRNA and protein in the progression of colorectal adenocarcinoma were investigated by reverse transcription polymerase chain reaction （ RT-PCR ） and immunohistochemistry. Results ： The mRNA expression of p27^kip1 and p53 in colorectal adenocarcinoma were lower than that in normal colon tissue （P〈0.01）;the level of skp2 mRNA expression in coloreclal adenocarcinoma was higher than that in normal colon tissue （P〈0.01）. Immunohistochemistry demonstrated that the positive rates of p27^kip1 was significantly lower in colorectal adenocarcinoma （25%） than in normal colon tissue（90%, P〈0.001 ） and eolorectal adenoma（55%, P〈0.001 ）;the positive rates of skp2 and p53 were significantly higher in colorectal adenocarcinoma （70% and 66.67% ） than in normal colon tissue （10% and 5%, P〈0.001 ） and in colorectal adenoma （50% and 25%, P〈0.001 ）. The expression level of p27^kip1 and skp2 protein was associated with the pathologic grade, invasion depth, clinical stage and lymph node metastasis of colorectal carcinoma（P〈0.05 ）. Overexpression of p53 was strongly related to the invasiveness, Dukes＇ stage, and metastasis of colorectal adenocarcinoma （P〈0.05）. There was an inverse correlation between the expression of p53 and p27^kip1. The expression level of p27^kip1 and skp2 were inversely correlated, while the expression level of p53 and skp2 protein were positively correlated. Conclusion： The expression of p27^kip1, skp2 and p53 might play critical roles in occurrence and development of colorectal tumor through their alteration.p27^kip1 expression is inversely correlated with p53 and skp2 expression, which suggests that p27^kip1 expression is regulated by p53 and skp2 in cell cycle progression.Combined detection of p27^kip1, skp2 and p53 gene is valuable for the assessment of malignant biological behavior in colorectal carcinoma