脾酪氨酸激酶基因甲基化与结直肠癌临床病理特征之间的关系

目的探讨脾酪氨酸激酶（Syk）基因甲基化、表达水平与结直肠癌患者临床病理特征及预后之间的关系。方法收集2001年1～12月间经手术治疗的120例结直肠癌标本．采用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）分析Syk基因的甲基化状态和表达情况，并分析Syk基因甲基化失表达与结直肠癌临床病理特衙和生存预后之间的关系。结果（1）120例结直肠癌患者中，48例肿瘤组织未检测到Syk基因的表达，而正常组织Syk基凶均表达；差异有统计学意义（X^2=60，P=0．000）。（2）发生甲基化的37例肿瘤组织中，Syk基因均失去表达。未发生甲基化的83例中，仅11例失表达；而癌旁匹配的正常组织均有表达。（3）Syk基因的甲基化状态与结直肠癌的淋巴结转移状态、病理分期密切相关，而与其他临床参数无关。（4）术后随访资料表明，Syk基因甲基化组患者的3年生存率明显低于未甲基化组（73．5％比95．7％，P=0．007）；而术后复发转移率明显高于未甲基化组（32．4％比8．4％，P=0．02）。结论Syk基因过甲基化失表达参与了结直肠癌的发生，导致结直肠癌侵袭性增强，患者术后复发转移率升高，3年生存率降低。

Association between hypermethylation of Syk gene and clinicopathological characteristics in colorectal cancer patients

OBJECTIVE: To investigate the association of the methylation status and expression level of Syk gene with the clinicopathological characteristics in colorectal cancer (CRC) patients. METHODS: Methylation-specific PCR(MSP) and RT-PCR techniques were used to analyze the methylation status and expression level of Syk gene in cancer and normal tissues of 120 CRC patients, meanwhile, association of the methylation status and expression level of Syk gene with the clinicopathological characteristics and the prognosis were studied. RESULTS: (1) Syk gene expression was not found in 48 cancer tissues out of 120 patients and was found in all the normal tissues.The difference was significant. (2) Loss of Syk expression was found in 37 patients with Syk hypermethylation, and in 11 out of 83 patients with Syk nonmethylation. (3) The methylation status of Syk gene was correlated with the lymph node status and the Dukes stage, but not with other clinicopathological parameters. (4) The follow-up data revealed that the 3-year survival of patients with Syk hypermethylation was lower than that of patients without Syk hypermethylation(73.5% vs.95.7%,P=0.007),and postoperative recurrence rate significantly increased in the Syk hypermethylation group (32.4% vs. 8.4%,P=0.02). CONCLUSION: Hypermethylation leads to silence of Syk gene involved in the initiation of colorectal cancer, which increases the infiltration of colorectal cancer cells, postoperative relapse and decreases the postoperative 3-year survival time.