目的探讨E3泛素连接酶家族的环指蛋白180(ring finger protein 180,RNF180)基因在胰腺癌中的甲基化情况及其表达调控机制。方法9个胰腺癌细胞系和112例原发性胰腺癌组织,以及半定量RT-PCR和甲基化特异性PCR(methylation specific PCR,M...目的探讨E3泛素连接酶家族的环指蛋白180(ring finger protein 180,RNF180)基因在胰腺癌中的甲基化情况及其表达调控机制。方法9个胰腺癌细胞系和112例原发性胰腺癌组织,以及半定量RT-PCR和甲基化特异性PCR(methylation specific PCR,MSP)技术被应用于RNF180基因的甲基化状态和表达调控研究。结果RNF180在CFPAC1、Panc5.04和PANC1细胞中高表达,MSP结果显示其启动子区域呈非甲基化状态;在T3M4和MIAPaCa2细胞中表达减少,其启动子区呈部分甲基化状态;在SW1990、Panc10.05、PANC3.11和AsPC1细胞中RNF180表达缺失,其启动子区呈完全甲基化状态。应用去甲基化药物5-aza-dc处理后,CFPAC1、Panc5.04和PANC1细胞中表达无变化,T3M4和MIAPaCa2细胞中表达增加,SW1990、Panc10.05、PANC3.11和AsPC1细胞中恢复表达。结果表明RNF180的表达受启动子区甲基化调控。RNF180基因在原发性胰腺癌中的甲基化率是31.25%(35/112)。RNF180甲基化与肿瘤分期有相关性(P<0.05),与年龄、性别、肿瘤大小、肿瘤位置、吸烟、饮酒等因素均无相关性(P均>0.05)。结论RNF180在胰腺癌中频繁发生甲基化,其表达受启动子区甲基化调节。RNF180甲基化是胰腺癌潜在的诊断和预后标志物。展开更多
Dear Editor,Early diagnosis is critical for successful treatment of gastric adenocarcinoma(GA).However,the sensitivities of tumor markers carcinoembryonic antigen(CEA),cancer antigen 19-9(CA19-9)and CA72-4 for GA dete...Dear Editor,Early diagnosis is critical for successful treatment of gastric adenocarcinoma(GA).However,the sensitivities of tumor markers carcinoembryonic antigen(CEA),cancer antigen 19-9(CA19-9)and CA72-4 for GA detection are approximately 20%[1],and the sensitivities of all markers combined for early gastric cancer detection is still very low[2].DNA methylation plays a major role in tumorigenesis and therefore has obvious potential as a non-invasive biomarker for cancer detection[3].Through genome-wide methylation analysis and histological verification,we previously identified ring finger protein 180(RNF180)as a novel preferentially methylated gene in GA[4,5].展开更多
目的观察胃癌患者血浆配对盒蛋白5(paired box protein 5,PAX5)与环指蛋白180(ring finger protein 180,RNF180)基因甲基化情况,探讨其与临床病理特征及预后的关系。方法110例胃癌患者为胃癌组,同期体检健康者50例为对照组,采用甲基化...目的观察胃癌患者血浆配对盒蛋白5(paired box protein 5,PAX5)与环指蛋白180(ring finger protein 180,RNF180)基因甲基化情况,探讨其与临床病理特征及预后的关系。方法110例胃癌患者为胃癌组,同期体检健康者50例为对照组,采用甲基化特异性PCR法检测血浆PAX5与RNF180基因甲基化状态,分析其与胃癌患者临床病理特征的关系。随访3年,采用Kaplan-Meier生存曲线分析PAX5、RNF180甲基化与患者预后的关系。结果胃癌患者血浆PAX5、RNF180基因启动子区甲基化发生率(70.00%、62.73%)高于对照组(32.00%、30.00%)(P<0.05),胃癌组TNM分期Ⅰ~Ⅱ期患者血浆PAX5、RNF180基因甲基化发生率(65.17%、57.30%)低于TNM分期Ⅲ~Ⅳ期患者(90.48%、85.71%)(P<0.05),胃癌组男性与女性、年龄<55岁与≥55岁、肿瘤直径<2.5 cm与≥2.5 cm、细胞低-中分化与高分化及有无淋巴结转移患者血浆PAX5、RNF180基因甲基化发生率比较差异均无统计学意义(P>0.05)。发生PAX5基因甲基化的胃癌患者3年生存率(68.83%)低于未发生甲基化患者(84.85%)(P<0.05),发生RNF180基因甲基化的胃癌患者3年总体生存率(73.91%)与未发生甲基化胃癌患者(73.17%)比较差异无统计学意义(P>0.05)。结论胃癌患者血浆PAX5与RNF180基因甲基化发生率增高,与肿瘤TNM分期有关,发生PAX5基因甲基化的患者3年总生存率低。展开更多
文摘目的探讨E3泛素连接酶家族的环指蛋白180(ring finger protein 180,RNF180)基因在胰腺癌中的甲基化情况及其表达调控机制。方法9个胰腺癌细胞系和112例原发性胰腺癌组织,以及半定量RT-PCR和甲基化特异性PCR(methylation specific PCR,MSP)技术被应用于RNF180基因的甲基化状态和表达调控研究。结果RNF180在CFPAC1、Panc5.04和PANC1细胞中高表达,MSP结果显示其启动子区域呈非甲基化状态;在T3M4和MIAPaCa2细胞中表达减少,其启动子区呈部分甲基化状态;在SW1990、Panc10.05、PANC3.11和AsPC1细胞中RNF180表达缺失,其启动子区呈完全甲基化状态。应用去甲基化药物5-aza-dc处理后,CFPAC1、Panc5.04和PANC1细胞中表达无变化,T3M4和MIAPaCa2细胞中表达增加,SW1990、Panc10.05、PANC3.11和AsPC1细胞中恢复表达。结果表明RNF180的表达受启动子区甲基化调控。RNF180基因在原发性胰腺癌中的甲基化率是31.25%(35/112)。RNF180甲基化与肿瘤分期有相关性(P<0.05),与年龄、性别、肿瘤大小、肿瘤位置、吸烟、饮酒等因素均无相关性(P均>0.05)。结论RNF180在胰腺癌中频繁发生甲基化,其表达受启动子区甲基化调节。RNF180甲基化是胰腺癌潜在的诊断和预后标志物。
基金supported by the National Key R&D Program of China(Grant no.2016YFC1303200,2022YFC2505100,2017YFC0908300,and 2018YFC1313101)Tianjin Key Medical Discipline(Specialty)Construction Project(Grant no.TJYXZDXK-009A)Beijing Munic-ipal Science&Technology Commission,Administrative Commission of Zhongguancun Science Park(Grant no.Z201100005420007).
文摘Dear Editor,Early diagnosis is critical for successful treatment of gastric adenocarcinoma(GA).However,the sensitivities of tumor markers carcinoembryonic antigen(CEA),cancer antigen 19-9(CA19-9)and CA72-4 for GA detection are approximately 20%[1],and the sensitivities of all markers combined for early gastric cancer detection is still very low[2].DNA methylation plays a major role in tumorigenesis and therefore has obvious potential as a non-invasive biomarker for cancer detection[3].Through genome-wide methylation analysis and histological verification,we previously identified ring finger protein 180(RNF180)as a novel preferentially methylated gene in GA[4,5].
文摘目的观察胃癌患者血浆配对盒蛋白5(paired box protein 5,PAX5)与环指蛋白180(ring finger protein 180,RNF180)基因甲基化情况,探讨其与临床病理特征及预后的关系。方法110例胃癌患者为胃癌组,同期体检健康者50例为对照组,采用甲基化特异性PCR法检测血浆PAX5与RNF180基因甲基化状态,分析其与胃癌患者临床病理特征的关系。随访3年,采用Kaplan-Meier生存曲线分析PAX5、RNF180甲基化与患者预后的关系。结果胃癌患者血浆PAX5、RNF180基因启动子区甲基化发生率(70.00%、62.73%)高于对照组(32.00%、30.00%)(P<0.05),胃癌组TNM分期Ⅰ~Ⅱ期患者血浆PAX5、RNF180基因甲基化发生率(65.17%、57.30%)低于TNM分期Ⅲ~Ⅳ期患者(90.48%、85.71%)(P<0.05),胃癌组男性与女性、年龄<55岁与≥55岁、肿瘤直径<2.5 cm与≥2.5 cm、细胞低-中分化与高分化及有无淋巴结转移患者血浆PAX5、RNF180基因甲基化发生率比较差异均无统计学意义(P>0.05)。发生PAX5基因甲基化的胃癌患者3年生存率(68.83%)低于未发生甲基化患者(84.85%)(P<0.05),发生RNF180基因甲基化的胃癌患者3年总体生存率(73.91%)与未发生甲基化胃癌患者(73.17%)比较差异无统计学意义(P>0.05)。结论胃癌患者血浆PAX5与RNF180基因甲基化发生率增高,与肿瘤TNM分期有关,发生PAX5基因甲基化的患者3年总生存率低。
