自噬相关基因LC3、Beclin-1与凋亡相关基因p53、BCL-2在大肠癌中的表达及意义

Expression and clinical significance of autophagy-related genes LC3,Beclin-1 and apoptosis-related genes p53,BCL-2 in colorectal carcinoma

目的检测自噬相关基因LC3、Beclin-1与凋亡相关基因p53、BCL-2在大肠癌、大肠腺瘤及正常大肠黏膜中的表达情况,探讨其与大肠癌发生、发展的相关性及意义。方法应用组织芯片技术和免疫组化SP法检测12例正常大肠黏膜、29例大肠腺瘤及115例大肠癌组织中LC3、Beclin-1、p53及BCL-2蛋白的表达水平,并结合临床病理因素进行分析。结果 LC3在大肠癌中的阳性率高于大肠腺瘤和正常大肠黏膜(P<0.01),且与大肠癌的组织学分化程度相关(P<0.05)。Beclin-1在大肠癌、大肠腺瘤组织中的表达高于正常大肠黏膜(P<0.01),但与大肠癌的组织学分化程度、Dukes分期及淋巴结转移无关(P均>0.05)。p53及BCL-2在正常大肠黏膜、大肠腺瘤及大肠癌中的表达逐渐增高(P<0.01),且与大肠癌的Dukes分期和淋巴结转移相关(P均<0.05)。经Spearman秩相关检验,Beclin-1蛋白与p53蛋白相关系数为0.224 3,成正相关表达(P<0.05)。结论在大肠癌中,自噬活性的上调与凋亡能力的下调并存;自噬相关基因LC3、Beclin-1与凋亡相关基因p53、BCL-2在大肠癌的发生、发展中起协调作用,对其联合检测有助于了解和判断大肠癌的进展程度及患者的预后情况。

Purpose To investigate the expression of autophagy-related genes LC3,Beclin-1 and apoptosis-related genes p53,BCL-2 in colorectal tumor tissues,and to explore their correlations with the tumorigenesis and development of colorectal carcinoma.Methods Tissue microarrays and immunohistochemistry were used to detect the expressions of LC3,Beclin-1,p53 and BCL-2 in 12 specimens of normal large intestinal mucosa,29 specimens of large intestinal adenoma and 115 specimens of colorectal carcinoma.Results LC3 expression was significantly higher in colorectal carcinoma than those in large intestinal adenoma and normal large intestinal mucosa（P0.01）.This high expression was associated with histological grade（P0.05）.The expression of Beclin-1 was higher in adenoma and colorectal carcinoma than those in normal large intestinal mucosa（P0.01）,but was not related to histological grade,Dukes stages or lymph metastasis（P0.05）.The expression of p53 and BCL-2 increased gradually in normal large intestinal mucosa,adenoma and colorectal carcinoma（P0.01）.The expressions of p53 and BCL-2 were correlated with Dukes stages and metastasis of lymph nodes（P0.05）.Beclin-1 expression was found to have positive correlation with p53 expression in colorectal carcinoma by the Spearman rank test（r=0.224 3,P0.05）.Conclusion The increase of autophagic capacity and decrease of apoptosis are both involved in the carcinogenesis of colorectal carcinoma.The autophagy-related genes LC3,Beclin-1 and apoptosis-related genes p53,BCL-2 coordinate with each other,and may be related to tumorigenesis and the development of colorectal carcinoma.The union examination of LC3,Beclin-1,p53 and BCL-2 protein may be helpful for the prognosis judgment of colorectal carcinoma.