CADM1与DAL-1/4.1B在结直肠癌中的表达及临床意义

Clinical significance of CADM1 and DAL-1/4.1B expression in colorectal carcinoma

目的:研究CADM1和DAL-1/4.1B两种抑癌基因在结直肠癌中的表达并分析两者之间及其与结直肠癌各临床病理参数之间的关系,探讨CADM1和DAL-1/4.1B在结直肠癌发生发展中的作用,为结直肠癌的基因治疗提出新的思路.方法:应用免疫组织化学(SABC法)检测30例结直肠癌组织,10例结直肠腺瘤组织,30例正常结直肠组织中CADM1和DAL-1/4.1B两种抑癌基因的表达;应用Western blot法检测30例结直肠癌组织,10例结直肠腺瘤组织,30例正常结直肠组织中CADM1及DAL-1/4.1B的表达,以图象分析软件进行半定量测定.结果:结直肠癌组织与结直肠腺瘤组织、正常对照组织中CADM1和DAL-1/4.1B表达阳性率差异有统计学意义(23.33%vs70.00%,86.67%;26.67%vs70.00%,83.33%,均P<0.05),Western blot条带经图象分析软件测得结直肠癌组织CADM1和DAL-1/4.1B吸光度与β-actin吸光度比值均显著低于结直肠腺瘤、正常对照组织(0.229±0.053vs0.299±0.068,0.418±0.081;0.223±0.052vs0.291±0.066,0.333±0.061,均P<0.05).CADM1和DAL-1/4.1B的表达部位和染色强度相似,半定量分析也显示两者呈正相关(r=0.710,P<0.05).CADM1和DAL-1/4.1B的表达与结直肠癌患者肿瘤分化程度、年龄、性别未见相关,而两者在Dukes分期C+D中的表达阳性率低于Dukes分期A+B差异有统计学意义(P<0.05).结论:结直肠癌中CADMl和DAL-1/4.1B基因均呈现失活和蛋白表达下调,CADM1与DAL-1/4.1B通过相互作用共同发挥其肿瘤抑制作用并参与结直肠癌的发生、发展.

AIM： To investigate the clinicopathological signif icance of the expression of cell adhesion molecule 1 （CADM1） and differentially expressed in adenocarcinoma of the lung/4.1B （DAL-1/4.1B） proteins in colorectal carcinoma,colorectal adenoma and normal colorectal mucosa.METHODS： Immunohistochemical staining was performed to detect the expression of CADM1 and DAL-1/4.1B proteins in 30 colorectal carcinoma specimens,10 colorectal adenoma specimens,and 30 normal colorectal mucosal specimens.Western blot was used to measure the protein expression of CADM1 and DAL-1/4.1B in the above specimens.Semiquantitation was performed using image analysis software.RESULTS： The positive rate of CADM1 and DAL-1/4.1B showed a downward trend in cancer ,colorectal adenoma and normal mu- cosa.The positive rates of CADM1 and DAL-1/4.1B were 23.33%/26.67% in colorectal carcinoma,70%/70% in colorectal adenoma,and 86.67%/83.33% in normal colorectal mucosa.Western blot analysis showed that the gray levels of CADM1 and DAL-1/4.1B in colorectal carcinoma were significantly lower than those in colorectal adenoma and normal colorectal mucosa （0.229 ± 0.053 vs 0.299 ± 0.068,0.418 ± 0.081;0.223 ± 0.052 vs 0.291 ± 0.066,0.333 ± 0.061,all P 0.05）.The expression and localization of CADM1 protein were parallel to those of DAL-1/4.1B,and the immunoreactive intensity of the two proteins was similar.Semiquantitative analysis showed that there was a positive correlation between the expression of CADM1 and DAL-1/4.1B （r = 0.710,P 〈0.05）.The expression of CADM1 and DAL-1/4.1B showed no signif icant association with age,gender or histological differentiation （all P〉 0.05）.The expression of CADM1 in Dukes stage C＋D carcinoma was much lower than that in Dukes stage A＋B carcinoma （P〈 0.05）.CONCLUSION： Down-regulation of CADM1 and DAL-1/4.1B protein expression occurs in colorectal carcinoma.Inactivation of CADM1 and DAL-1/4.1B genes may be associated with the development of colorectal carcinoma.CADM1 and DAL-1/4.1B can interact with each other during colorectal carcinogenesis.