AIM:To assess diagnostic accuracy of Ras association domain family 1A(RASSF1A)promoter methylation in body fluids(serum,plasma and whole blood)for hepatocellular carcinoma(HCC).METHODS:Relative information about study...AIM:To assess diagnostic accuracy of Ras association domain family 1A(RASSF1A)promoter methylation in body fluids(serum,plasma and whole blood)for hepatocellular carcinoma(HCC).METHODS:Relative information about study characteristics and incidence of RASSF1A methylation was collected.Quality of all included studies was evaluated by Quality Assessment of Diagnostic Accuracy Studies-2.Sensitivity and specificity were pooled using a randomeffect model,and a summary receiver operating characteristic curve was used to demonstrate the overall diagnostic performance.Positive likelihood ratio(PLR),negative likelihood ratio(NLR),and diagnostic odds ratio(DOR)with 95%CI were also calculated.Meta-regression was applied to analyze observed heterogeneity,and Deeks’test was performed to detect publication bias.RESULTS:After a systematic literature review,seven studies with a total of 302 cases of HCC and 250 cases of chronic liver diseases were included in the analysis.The pooled sensitivity and specificity were 0.70(95%CI:0.49-0.85)and 0.72(95%CI:0.54-0.85),respectively.The PLR was 2.51(95%CI:1.64-3.86),NLR was 0.41(95%CI:0.25-0.68),and DOR was 6.13(95%CI:3.17-11.84).Theχ2values of sensitivity,specificity,PLR,NLR and DOR were 59.41(P<0.001),50.50(P<0.001),17.40(P=0.010),31.24(P<0.001)and80.51(P<0.001),respectively.The area under the curve was 0.77(95%CI:0.73-0.81).Three factors were analyzed by univariate meta-regression and none was significant to interpret the observed heterogeneity(P>0.05).No significant publication bias was detected by Deeks’test(P=0.346).CONCLUSION:We showed the potential diagnostic value of RASSF1A methylation in body fluids in HCC patients and it may improve diagnostic accuracy combined with theα-fetoprotein test.展开更多
目的:探讨卵巢癌组织和腹腔冲洗液中Ras相关区域家族1A(Ras association domain family 1A,RASSF 1A)基因启动子异常甲基化状况及其在卵巢癌诊断中的价值。方法:采用甲基化特异性PCR方法检测42例卵巢癌组织、腹腔冲洗液或腹腔积液、11...目的:探讨卵巢癌组织和腹腔冲洗液中Ras相关区域家族1A(Ras association domain family 1A,RASSF 1A)基因启动子异常甲基化状况及其在卵巢癌诊断中的价值。方法:采用甲基化特异性PCR方法检测42例卵巢癌组织、腹腔冲洗液或腹腔积液、11例正常卵巢组织和19例良性病变卵巢组织中RASSF 1A基因启动子区甲基化状态。结果:42例卵巢癌组织中RASSF 1A基因启动子区甲基化发生率为38.1%,11例正常卵巢组织和19例良性卵巢组织中RASSF 1A基因启动子区无甲基化,差异有统计学意义(P<0.01)。临床分期Ⅲ期和Ⅳ期的卵巢癌组织中RASSF 1A基因启动子区甲基化发生率为54.2%,高于临床Ⅰ期和Ⅱ期者16.6%(P<0.05)。淋巴结阳性者癌组织中RASSF 1A基因启动子区甲基化发生率56.5%,高于淋巴结阴性者15.8%。腹腔冲洗液或腹腔积液细胞学阳性者癌组织中RASSF 1A基因启动子区甲基化发生率为74.1%,高于腹腔冲洗液或腹腔积液细胞学阴性者33.3%(P<0.01)。结论:RASSF 1A基因甲基化在卵巢癌患者中具有较高的发生率,检测卵巢癌组织和腹腔冲洗液或腹腔积液中RASSF 1A基因的甲基化状态对卵巢癌的诊断和判断预后具有一定的价值。展开更多
目的:检测Ras相关区域家族1A(Ras association domain family 1A,RASSF1A)在胰腺癌细胞株中的甲基化和表达状态,探讨其启动子异常甲基化在胰腺癌发病过程中的作用。方法:采用重亚硫酸盐测序PCR(bisulfite genomic sequencing PCR,BSP)联...目的:检测Ras相关区域家族1A(Ras association domain family 1A,RASSF1A)在胰腺癌细胞株中的甲基化和表达状态,探讨其启动子异常甲基化在胰腺癌发病过程中的作用。方法:采用重亚硫酸盐测序PCR(bisulfite genomic sequencing PCR,BSP)联合TA克隆测序检测胰腺癌细胞株PANC-1及胰腺癌组织、癌旁组织及正常胰腺组织中RASSF1A启动子区CpG岛的甲基化状态,以甲基化酶抑制剂5-aza-2-deoxycitydine(5-aza-dC)处理PANC-1,观察处理前后甲基化率变化情况,逆转录PCR观察RASSF1A的mRNA表达情况。结果:在PANC-1细胞中RASSF1A启动子的甲基化率平均为100.00%,在正常胰腺、癌旁及癌组织中平均分别为1.79%、93.75%和100.00%,与正常胰腺组织相比,胰腺癌旁及癌组织的RASSF1A启动子甲基化率明显增高(P<0.01),而癌旁及癌组织之间无明显差异(P>0.05)。在PANC-1细胞、胰腺癌组织及癌旁组织中RASSF1A基因无表达,在正常胰腺组织中RASSF1A基因呈阳性表达;PANC-1细胞经5-aza-dC处理后,RASSF1A的甲基化率下降(88.89%,P<0.05),mRNA表达无变化。结论:胰腺癌细胞株PANC-1及癌组织、癌旁组织RASSF1A基因表达与启动子区甲基化状态有关,启动子区的高甲基化导致PANC-1中RASSF1A基因的表达沉默。该基因异常甲基化有望成为胰腺癌的早期诊断指标和治疗靶点。展开更多
基金Supported by Key Project of Chinese Ministry of Science and Technology,No.2012ZX10002007 and No.2013ZX10002001National Natural Science Foundation of China,No.81171579and No.81201287Natural Science Foundation of Shandong Province,China,No.ZR2010HM070 and No.ZR2010HQ040
文摘AIM:To assess diagnostic accuracy of Ras association domain family 1A(RASSF1A)promoter methylation in body fluids(serum,plasma and whole blood)for hepatocellular carcinoma(HCC).METHODS:Relative information about study characteristics and incidence of RASSF1A methylation was collected.Quality of all included studies was evaluated by Quality Assessment of Diagnostic Accuracy Studies-2.Sensitivity and specificity were pooled using a randomeffect model,and a summary receiver operating characteristic curve was used to demonstrate the overall diagnostic performance.Positive likelihood ratio(PLR),negative likelihood ratio(NLR),and diagnostic odds ratio(DOR)with 95%CI were also calculated.Meta-regression was applied to analyze observed heterogeneity,and Deeks’test was performed to detect publication bias.RESULTS:After a systematic literature review,seven studies with a total of 302 cases of HCC and 250 cases of chronic liver diseases were included in the analysis.The pooled sensitivity and specificity were 0.70(95%CI:0.49-0.85)and 0.72(95%CI:0.54-0.85),respectively.The PLR was 2.51(95%CI:1.64-3.86),NLR was 0.41(95%CI:0.25-0.68),and DOR was 6.13(95%CI:3.17-11.84).Theχ2values of sensitivity,specificity,PLR,NLR and DOR were 59.41(P<0.001),50.50(P<0.001),17.40(P=0.010),31.24(P<0.001)and80.51(P<0.001),respectively.The area under the curve was 0.77(95%CI:0.73-0.81).Three factors were analyzed by univariate meta-regression and none was significant to interpret the observed heterogeneity(P>0.05).No significant publication bias was detected by Deeks’test(P=0.346).CONCLUSION:We showed the potential diagnostic value of RASSF1A methylation in body fluids in HCC patients and it may improve diagnostic accuracy combined with theα-fetoprotein test.
文摘目的:检测Ras相关区域家族1A(Ras association domain family 1A,RASSF1A)在胰腺癌细胞株中的甲基化和表达状态,探讨其启动子异常甲基化在胰腺癌发病过程中的作用。方法:采用重亚硫酸盐测序PCR(bisulfite genomic sequencing PCR,BSP)联合TA克隆测序检测胰腺癌细胞株PANC-1及胰腺癌组织、癌旁组织及正常胰腺组织中RASSF1A启动子区CpG岛的甲基化状态,以甲基化酶抑制剂5-aza-2-deoxycitydine(5-aza-dC)处理PANC-1,观察处理前后甲基化率变化情况,逆转录PCR观察RASSF1A的mRNA表达情况。结果:在PANC-1细胞中RASSF1A启动子的甲基化率平均为100.00%,在正常胰腺、癌旁及癌组织中平均分别为1.79%、93.75%和100.00%,与正常胰腺组织相比,胰腺癌旁及癌组织的RASSF1A启动子甲基化率明显增高(P<0.01),而癌旁及癌组织之间无明显差异(P>0.05)。在PANC-1细胞、胰腺癌组织及癌旁组织中RASSF1A基因无表达,在正常胰腺组织中RASSF1A基因呈阳性表达;PANC-1细胞经5-aza-dC处理后,RASSF1A的甲基化率下降(88.89%,P<0.05),mRNA表达无变化。结论:胰腺癌细胞株PANC-1及癌组织、癌旁组织RASSF1A基因表达与启动子区甲基化状态有关,启动子区的高甲基化导致PANC-1中RASSF1A基因的表达沉默。该基因异常甲基化有望成为胰腺癌的早期诊断指标和治疗靶点。
