【摘要】 目的研究SALL3启动子高甲基化与原发性肝细胞癌(HCC)患者临床病理特征的关系。方法应用甲基化特异性PCR(MSP)技术分析283对HCC及其相邻非肿瘤组织中SALL3的甲基化状态,评估SALL3启动子甲基化与临床特征的相关性。结果肝细胞癌中SALL3启动子区甲基化率(38.87%)高于相邻癌旁组织(9.89%),差异有统计学意义(χ~2=64.43,P<0.000 1)。单因素分析显示,不同年龄、性别、HBV病毒感染状况、肿瘤大小的肝癌患者SALL3基因甲基化率差异无统计学意义(P>0.05),但不同肝癌细胞分化程度(χ~2=3.046,P=0.018 9)、临床分期(χ~2=4.684,P=0.030 4)、门静脉瘤栓侵犯(χ~2=14.930,P=0.000 1)的肝癌患者SALL3基因甲基化率差异有统计学意义。单因素Cox回归分析显示SALL3基因甲基化(OR=1.73,95%CI:1.28~2.33,P=0.002 6)、肝硬化(OR=1.56,95%CI:1.11~2.18,P=0.009 6)、临床分期(OR=1.63,95%CI:1.36~1.94,P=0.000 0)是患者5年生存的影响因素。多因数Cox回归分析证实SALL3基因甲基化(OR=1.41,95%CI:1.02~1.94,P=0.035 7)、临床分期(OR=1.73,95%CI:1.39~2.01,P=0.000 0)是影响HCC患者术后生存期的独立危险因素。SALL3启动子甲基化的HCC患者术后生存时间明显短于非甲基化HCC患者[(20.37±3.5)月vs.(30.77±5.5)月,P=0.002 4)]。结论 SALL3基因启动子区甲基化状态是检测原发性肝细胞癌和预后不良的潜在生物标志物。更多还原

【Abstract】 Objective To study the relationship between hypermethylation in SALL3 promoter and clinicopathological features in patients with primary hepatocellular carcinoma( HCC). Methods Methylation statuses of SALL3 promoter in 283 pairs of HCC and its adjacent non-tumor tissues were analyzed by methylation specific PCR( MSP) technique,and the correlation between SALL3 promoter methylation and clinical characteristics was evaluated. Results The methylation rate of SALL3 promoter region was higher in HCC than in adjacent paracancerous tissues( 38.87% vs. 9.89%),showing a statistically significant difference( χ2=64.43,P<0.000,1). Univariate analysis revealed that the methylation rate of SALL3 gene showed no statistically significant difference among HCC patients with different ages,genders,hepatitis B virus infectious statuses and tumor sizes( P>0.05),but showed statistically significant differences among HCC patients with different conditions of differentiation of HCC cells( χ2= 3. 046,P =0. 018,9),clinical stages( χ2= 4.684,P = 0.030,4) and portal vein thrombosis( χ2= 14.930,P = 0.000,1). Univariate COX regression analysis indicated that SALL3 gene methylation( OR = 1. 73,95% CI: 1. 28-2. 33,P = 0. 002,6),cirrhosis( OR = 1. 56,95%CI: 1.11-2.18,P = 0.009,6) and clinical stage( OR = 1.63,95%CI: 1.36-1.94,P = 0.000,0) were the factors influencing the patients’ 5-year survival. Multivariate COX regression analysis confirmed that SALL3 gene methylation( OR = 1.41,95% CI:1. 02-1.94,P = 0.035,7) and clinical stage( OR = 1.73,95%CI: 1.39-2.01,P = 0.000,0) were the independent risk factors affecting the HCC patients’ postoperative survival time. The postoperative survival time was significantly shorter in HCC patients with methylated SALL3 promoter than those with unmethylated SALL3 promoter(( 20.37 ± 3. 5) months vs.( 30. 77 ± 5. 5) months,P =0. 002,4). Conclusions The methylation status of promoter region of SALL3 gene is a potential biomarker for detecting primary HCC and poor prognosis.更多还原