P27基因甲基化与结直肠癌发生发展及临床生物学行为的关系

Relationship between methylation of P27 gene and colorectal carcinogenesis and biological behavior.

目的研究P27基因在结直肠癌发生过程中的蛋白表达和基因启动子区CpG岛甲基化状态的变化及意义。方法采用免疫组织化学染色和甲基化特异性PCR系统检测结直肠癌患者手术切缘黏膜上皮、癌旁组织、癌组织各56例、腺瘤42例中p27蛋白的表达和基因甲基化状态的变化。结果p27蛋白在结直肠癌患者手术切缘黏膜上皮的表达率最高(77%),随病变进展其表达率呈下降趋势,其在癌旁组织(59%)、腺瘤(57%)和癌组织(32%)中的表达与手术切缘黏膜上皮相比及癌与癌旁组织或腺瘤相比差异均有统计学意义;在结直肠癌发生过程中,P27基因甲基化程度呈增加趋势,且在各病变阶段与蛋白的表达呈明显负相关,其甲基化程度还与淋巴结转移密切相关。结论P27基因异常甲基化是p27失活的主要机制,与结直肠癌的发生、发展密切相关,可作为结直肠癌早期诊断、临床生物学行为和预后判断的重要参考指标。

Objective:To investigate the expression of p27 protein and the change of the methylation status of CpG island in p27 promotor region, and to analyze their role in colorectal carcinogenesis. Methods:Immunohistochemical staining and methylation-specific PCR were used to detect the expression and methylation status of p27 in normal colorectal mucosa epithelium (n=56), adjacent tissue of carcinoma (n=56), adenoma (n=42) and carcinoma (n=56), respectively. Results:Positive rate of p27 protein (77%) was the highest in normal colorectal mucosa epithelium, and decreased with progression. Its expression was significantly reduced in adjacent tissue of carcinoma (59%), adenoma (57%) and carcinoma (32%) compared with normal mucosa epithelium, and there was a significant difference between carcinoma and adjacent tissue or adenoma. For the level of methylation of p27, an increased tendency was found during colorectal carcinogenisis, and there was significant inverse correlation between abnormal methylation of p27 and its expression. The level of methylation of p27 was correlated with lymphatic metastasis. Conclusion:Abnormal methylation of P27 gene is the main mechanism of p27 inactivation and it was closely associated with colorectal carcinogenesis. So it may be used as an important parameter in early diagnosis and evaluating the biological characteristics and prognosis of colorectal carcinoma. [