抑癌基因TIP30启动子甲基化对大肠癌诊断及预后的影响

目的研究TIP30启动子甲基化在大肠癌与配对正常大肠黏膜中的表达差异，分析TIP30启动子甲基化状态与患者临床病理特征间的关系。方法对我院2009-2010年收治的50例大肠癌患者的手术切除标本和配对正常大肠黏膜组织，采用甲基化特异性PCR方法检测TIP30基因启动子甲基化状态。结果大肠癌TIP30启动子高甲基化与患者淋巴结转移情况（P=0.003）、CEA水平（P=0.005）及临床分期（P=0.048）之间存在显著相关性，与病变部位（结肠与直肠）之间未见显著相关性（P=0.309）。此外，TIP30启动子高甲基化在血清CEA水平较高（＞15 ng/ml）的患者中比血清CEA水平较低（＜15 ng/ml）的患者中更常见（P=0.005）。结论TIP30启动子高甲基化与大肠癌淋巴结转移、CEA水平及临床分期呈正相关，与病变部位无明显相关性。TIP30启动子甲基化有望成为一种新的大肠癌分子诊断肿瘤标志物，用于大肠癌患者的早期诊断与预后判断。

Methylation of Tumor Suppressor Gene TIP30 in Promoter Region for Colorectal Cancer Diagnosis and Prognosis

Objective
To investigate the difference of promoter methylation of TIP30 gene between colorectal cancer (CRC) and the normal colorectal samples.To analyze the relationship between TIP30 gene methylation and the clinicopathological features of patients.
Methods
The difference of methylation status of TIP30 between 50 cases of patients with CRC and the paired normal colorectal samples from 2009 to 2010 in the hospital was detected using methylation-specific PCR.
Results
There was a significant correlation between hypermethylation of TIP30 and unfavorable variables,including lymph nodes metastasis (P=0.003),CEA levels (P=0.005),and advanced colorectal cancer (P=0.048).There was no obvious difference between colon and rectal tissues in carcinoma samples (P=0.309).Interestingly,hypermethylation of TIP30 was more frequently founded（P=0.005） in the tumors from patients with higher serum level of CEA (>15 ng/ml) than that from the patients with lower serum level of CEA (<15 ng/ml).
Conclusion
This study showed a significant positive correlation between hypermethylation of TIP30 promoter and nodal metastasis,CEA levels,and advanced CRC.There was no obvious difference between colon and rectal tissues in carcinoma samples.Our research suggested that hypermethylation of TIP30 might be used as a new tumor marker for CRC molecular diagnosis and prognosis.