肝细胞癌Period1 表达与预后的关系

目的：探讨Period1在肝细胞癌（HCC）组织中的表达及意义。方法：用RT-PCR与Western blot法检测30例HCC组织与其癌旁肝组织及5例正常肝组织中Period1 mRNA与蛋白表达；甲基化特异性PCR检测HCC组织与癌旁肝组织中Period1启动子甲基化水平；免疫组化检测67例HCC组织及其癌旁肝组织石蜡切片中Period1蛋白的表达；分析Period1的表达与HCC患者临床病理特征及预后的关系。结果：HCC组织Period1 mRNA和蛋白的表达水平均较癌旁肝组织与正常肝组织明显降低（均P<0.05），而两者在癌旁肝组织与正常肝组织间差异无统计学意义（均P>0.05）；HCC组织Period1启动子甲基化水平较其癌旁肝组织明显增高（均P<0.05）。HCC组织石蜡切片中Period1阳性表达率为47.8%，而癌旁肝组织阳性表达率为83.6%，差异有统计学意义（P<0.05）；Period1表达与HCC分化程度、结节数目、有无静脉浸润有关（均P<0.05）；Period1阳性表达HCC患者中位复时间与中位生存时间均明显短于阳性者（均P<0.05）。结论：Period1在肝癌中表达下调可能与HCC的发生发展和侵袭转移密切相关；启动子甲基化可能是Period1表达下调的重要机制。

Relationship between Period1 expression and prognosis in hepatocellular carcinoma

Objective: To investigate the Period1 expression in hepatocellular carcinoma (HCC) tissue and its significance.Methods: The Period1 mRNA and protein expressions in the specimens of 30 HCC tissues along with their adjacent liver tissues and 5 normal liver tissues were detected by RT-PCR method and Western blot analysis, and the methylation level in the promoter sequences of Period1 in HCC tissues and their adjacent liver tissues was determined by methylation-specific PCR. Period1 protein expression in 67 paraffin-embedded HCC tissue and adjacent liver tissue samples were examined by immunohistochemical staining, and the relations of Period1 expression with the clinicopathologic characteristics and prognosis of the patients were analyzed.Results: Both the Period1 mRNA and protein expressions in HCC tissue were significantly lower than those in the adjacent liver tissue or normal liver tissue (all P<0.05), but there was no statistical difference between the adjacent liver tissue and normal liver tissue (both P>0.05); the methylation level in the promoter sequences of Period1 in HCC tissue was significantly higher than that in the adjacent liver tissue (P<0.05); Period1 positive expression rate was 47.8% for HCC tissue and 83.6% for adjacent tissues in the paraffin-embedded samples, and the difference had statistical significance (P<0.05); Period1 expression was related to the degree of differentiation of HCC, tumor number, and vascular invasion (all P<0.05); the median time to recurrence and median survival time in HCC patients with negative Period1 expression were significantly reduced compared with those with positive Period1 expression (both P<0.05).Conclusion: Down-regulated Period1 expression may be closely related to the occurrence and development as well as invasion and metastasis of HCC, and promoter methylation is possibly an important mechanism for Period1 down-regulation.