结直肠癌侵袭性与脾酪氨酸激酶基因Syk启动子甲基化的关系

Hypermathylation of SYK gene in promoter region and its association with invasion in colorectal cancer

目的 探讨脾酪氨酸激酶 (Syk)基因启动子甲基化与结直肠癌侵袭转移之间的关系。方法 采用巢式双重甲基化特异性聚合酶链反应 (MSP)和逆转录 聚合酶链反应 (RT PCR)的方法检测Syk基因在 12 0例结直肠癌肿瘤组织、癌旁正常组织中的甲基化和表达情况。 结果 12 0例结直肠癌患者中 ,48例未检测到SykmRNA的表达 ,而癌旁正常组织均有表达。癌旁正常组织未检测到Syk基因启动子甲基化 ,3 7例肿瘤组织发生Syk基因启动子甲基化(3 0 .8% ) ,癌组织Syk基因启动子甲基化率显著增高 (P <0 .0 0 0 5 )。在淋巴结转移的 5 6例中 ,2 4例发生Syk基因启动子甲基化 ,而无淋巴结转移的 64例中 ,13例发生甲基化 ,有淋巴结转移的Syk基因启动子甲基化发生率显著高于无淋巴结转移组 (P =0 .0 0 8)。发生甲基化的肿瘤组织中 ,均无SykmRNA的表达。结论 结直肠癌中 ,SYK基因启动子过甲基化导致其mRNA的失表达 ,从而引起结直肠癌的侵袭性增强 ,它可能是结直肠癌发生侵袭转移的又一种机制。

Objective To investigate the correlation between promoter region hypermethylation of Syk gene and invasion of colorectal cancer.Methods Nest duplicated methylation specific PCR (MSP) and RT PCR techniques were used to detect methylation of Syk gene promoter region and Syk mRNA expression in the specimens of tumor tissue and adjacent normal tissue from 120 colorectal cancer patients.Results The expression of Syk gene was detected in all normal colorectal tissues,and only in tumor tissues in 48 of 120 cases.No methylation of Syk promoter region was detected in adjacent normal tissues,but hypermethylation of syk gene in promoter region was found in 37 of 120 colorectal cancer patients.The rate of methylation of Syk gene in cancerous tissues was higher than that in adjacent normal tissues ( P < 0.0005). Syk gene hypermethylation was found in 24 of 56 cases with lymph node metastasis,while only 13 of 64 cases without lymph node metastasis.There was significant difference between the two groups ( P = 0.0008). The expression of Syk mRNA was not detected in methylated cancer tissues.Conclusion Hypermethylation of SYK gene in promoter region,leading to the loss of SYK gene expression,may be another mechanism for invasion of colorectal cancers.