不同分期结直肠癌组织中CA1基因表达与临床病理的相关性探讨

Expression and clinical significance of carbonic anhydrase 1 in different clinical stages of colorectal cancers

目的 探讨碳酸酐酶1（CA1）在不同临床分期结直肠癌组织中的表达模式及其与结直肠癌患者临床病理特征的相关性.方法 采用实时定量PCR检测基因水平CA1的表达.分别采用蛋白免疫印迹和免疫组织化学染色法检测蛋白水平CA1的表达.结果 在62例冰冻组织样本中,基因水平及蛋白水平的CA1在癌远端正常结直肠黏膜中的表达显著高于癌组织（P＜0.01）,不同临床分期结直肠癌组织中CA1表达呈折线模式,基因水平CA1的表达模式与蛋白水平相似,且均在进展期（Ⅲ期＋Ⅳ期）结直肠癌组织中下调更为明显.免疫组化在103例石蜡包埋组织中检测发现,CA1在癌远端正常上皮细胞中阳性表达率90.29％,显著高于癌组织中的阳性表达率（62.14％,P＜0.01）.CA1在高分化、中分化及低分化结直肠癌组织中的阳性表达率分别为90％、62.79％和5％,两两比较差异具有统计学意义（P＜0.01）.在存在淋巴结及远端转移的结直肠癌组织中CA1表达显著低于无转移组（37.14％vs 75％,P＜0.01）.CA1表达缺失与结直肠癌患者预后差相关,CA1阴性表达组5年生存率仅为8％,而阳性表达组患者5年生存率为92.86％,两者比较差异具有统计学意义（P＜0.01）.结论 CA1在基因水平和蛋白水平具有相似的表达模式.在结直肠癌组织中表达下调甚至缺失.CA1的表达下调与患者存在淋巴结转移或远处转移有关.癌组织分化程度越低,CA1表达下调越明显,越易发生转移,预后越差.

Objective To investigate the expression pattern of carbonic anhydrase 1 （CA1） in different clinical stages of color ectal cancers and the correlation between CA1 expression and pathologic characteristics of colorectal cancer.Methods The expression of CA1 in genetic level was detected by real-time quantitative polymerase chain reaction （PCR） and the expression of CA1 in protein level was detected by Western blot and immunohistochemical staining.Results The expression pattern of CA1 in the protein level was very similar to the genetic level.It had a very low expression level in carcinoma tissue,especially at stages Ⅲ and Ⅳ （P 〈0.01）,CA1 had significantly lower expression level in the colorectal patients with metastasis （P 〈0.01）.CA1 was gradually decreased from well-differentiation tissue to poorly-differentiation tissue with a significant difference between well-differentiated adenocarcinoma and poorly-differentiated adenocarcinoma （P 〈 0.01）.Kaplan-Meier survival analysis showed that the expression of CA1 was extremely related to colorectal carcinoma （CRC） prognosis.The 5-year survival rate was only 8% in the CA1 negative expression group,and the 5-year survival rate of the patients with CA1 positive expression was 92.86% （P 〈 0.01）.Conclusions CA1 had the similar expression patterns at genetic and protein levels.In the colorectal cancer tissue,the expression of CA1 was downregulated and even missing.CA1 had significantly lower expression level in the advanced colorectal cancers with metastasis and poorly differentiated colorectal cancer tissues.The patients with lower CA1 expression level had the worse prognosis.