肿瘤相关基因RASAL1在结肠癌中的表达及临床意义

Clinical significance of RASAL1 expression in colorectal carcinoma

目的:探讨Ras三磷酸鸟苷酶激活样蛋白(RASAL1)及基因在人结肠癌中的表达及其与临床病理参数间的关系.方法:收集2009-04/2010-05经手术切除的结肠腺癌标本50例作为研究组,相应正常组织为对照组,做成蜡块标本;其中20例另取其癌组织、癌旁组织及正常组织的新鲜标本;用免疫组织化学染色观察50例蜡块标本RASAL1蛋白的表达;用RT-PCR检测20例新鲜标本RASAL1 mRNA的表达,并分析其与临床病理参数的关系.结果:RASAL1蛋白主要在细胞质中表达;RASAL1蛋白在结肠癌中的阳性表达率明显低于癌旁组织及正常组织[46%(23/50)vs85%(17/20),96%(48/50),均P<0.05];RASAL1 mRNA在结肠癌中的阳性表达率较癌旁组织及正常组织明显减低[50%(10/20)vs90%(18/20),95%(19/20),均P<0.05],RASAL1蛋白与mRNA的表达呈明显正相关(r=0.686,P<0.01),与肿瘤的分化程度(P<0.05)、侵袭深度(P<0.01)、淋巴结转移(P<0.05)、TNM分期(P<0.05)呈负相关.结论:RASAL1在结肠腺癌组织中低表达,且与分化程度及进展阶段负相关;RASAL1有可能成为结肠癌治疗的一个新靶点.

AIM：To investigate the expression of RASAL1（Ras GTPase-activating-like protein 1） mRNA and protein in human colorectal carcinoma（CRC） and to analyze its correlation with tumor clinicopathological features.METHODS：Fifty paraffin-embedded surgical CRC specimens,matched tumor-adjacent tissue specimens,and normal colorectal tissue specimens were used to detect the distribution of RASAL1 by immunohistochemistry（IHC）.Twenty fresh CRC specimens,matched tumoradjacent tissue specimens,and normal colorectal tissue specimens were used to determine the levels of RASAL1 mRNA expression by RT-PCR.The correlation between RASAL1 expression and tumor clinicopathological parameters was analyzed.RESULTS：RASAL1 was mainly localized in the cytoplasm of glands cells.The positive rate of RASAL1 protein expression in CRC was significantly lower than those in tumor-adjacent tissue and normal colorectal tissue [46%（23/50） vs 85%（17/20）,96%（48/50）,both P 0.05].The positive rate of RASAL1 mRNA expression was also significantly lower in CRC than in tumoradjacent tissue and normal colorectal tissue [50%（10/20） vs 90%（18/20）,95%（19/20）,both P 0.05].The expression of RASAL1 protein was positively related with that of RASAL1 mRNA（r = 0.686,P 0.01）,but negatively with tumor differentiation degree（P 0.05）,invasive depth（P 0.01）,lymph node metastasis（P 0.05）,and TNM stage（P 0.05）.CONCLUSION：The expression of RASAL1 mRNA and protein is reduced in CRC.RASAL1 expression is negatively related to tumor progression.RASAL1 may be a novel therapeutic target for CRC.