目的:研究SFRPs家族中SFRP1、SFRP2、SFRP4、SFRP5基因启动子区甲基化状况,探讨基因的甲基化与肾透明细胞癌发生发展的关系。方法:采用甲基化特异性PCR(methylation specific PCR,MSP)方法检测66例肾透明细胞癌及30例癌旁组织中SFRP1、S...目的:研究SFRPs家族中SFRP1、SFRP2、SFRP4、SFRP5基因启动子区甲基化状况,探讨基因的甲基化与肾透明细胞癌发生发展的关系。方法:采用甲基化特异性PCR(methylation specific PCR,MSP)方法检测66例肾透明细胞癌及30例癌旁组织中SFRP1、SFRP2、SFRP4、SFRP5基因启动子区甲基化状态及其与临床病理学资料之间的关系。结果:肾透明细胞癌组织中SFRP1、SFRP2、SFRP4、SFRP5基因甲基化率分别为77.3%(51/66)、72.7%(48/66)、59.1%(39/66)、69.7%(46/66),均显著高于相应的癌旁组织,结果有统计学意义(P<0.05)。与临床病理学资料相联系,肾透明细胞癌组织中SFRP1、SFRP5基因甲基化与肿瘤TNM分期相关;SFRP4基因甲基化与肿瘤的病理学分级相关(P<0.05)。结论:SFRP1、SFRP2、SFRP4、SFRP5基因的甲基化均可能参与肾透明细胞癌的发生。SFRP1、SFRP5基因甲基化可能与肾透明细胞癌的发展,浸润和转移有关。SFRP4基因甲基化可能与肾透明细胞癌的恶性行为有关。展开更多
Objective：To investigate the feasibility of the combination of detecting hypermethylated secreted frizzled-related protein 1 （SFRP1） and secreted frizzled-related protein 2（SFRP2） in feces as a panel of biomarker...Objective：To investigate the feasibility of the combination of detecting hypermethylated secreted frizzled-related protein 1 （SFRP1） and secreted frizzled-related protein 2（SFRP2） in feces as a panel of biomarkers for colorectal cancer（CRC） screening. Methods： Methylation-specific PCR（MSP） was performed to analyze methylation status of SFRP1 and SFRP2 in a blinded fashion in tumor tissues and in matched stool samples from 39 patients with primary CRC, 34 patients with adenomas, 17 patients with hyperplastic polyps and 20 endoscopically normal subjects as normal controls. Simultaneously we analyzed the correlation of hypermethylated SFRP1 and SFRP2 with the clinicopathological features of CRC. Results：Hypermethylated SFRP1 was detected in 92.3%, 76.5%, 47.1% of tissue samples and in 89.7%, 64.7%, 35.3% of matched fecal samples from CRC, adenoma and hyperplastic polyp, respectively. Hypermethylated SFRP2 was detected in 87.2%, 67.6%, 35.3% of tissue samples and in 82.1%, 55.9%, 29.4% of matched fecal samples from CRC, adenoma and hyperplastic polyp, respectively. Of these two genes, at least one hypermethylated was 94.9%, 82.4%, 52.9% in tissue samples and 92.3%,73.5%, 47.1% in matched fecal samples from CRC, adenoma and hyperplastic polyp, respectively. In contrast, no hypermethylated SFRP1 and SFRP2 were detected in mucosa tissues of normal controls, only 2 cases of fecal samples was detected with hypermethylated SFRP1 and another 1 case was detected with hypermethylated SFRP2. Moreover, no significant associations were observed between hypermethylated SFRP1,SFRP2 and clinicopathological features of CRC. Conclusion： Hypermethylation of SFRP1 and SFRP2 in feces are novel epigenetic biomarkers of CRC and carded high potential for the remote detection of CRC as non-invasive screening method, and combined analysis of hypermethylated SFRP1 and SFRP2 in fecal could further increase the detection rate of CRC and premalignant lesions.展开更多
Secreted frizzled-related protein 2 （SFRP2）, a member of the SFRPs family, is associated with cell growth and differentiation in myogenesis. Our previous study suggested that SFRP2 was a potential target of microRNA...Secreted frizzled-related protein 2 （SFRP2）, a member of the SFRPs family, is associated with cell growth and differentiation in myogenesis. Our previous study suggested that SFRP2 was a potential target of microRNA （miRNA）-I/206, which was considered as myomiRs. To further explore the biological function and regulation mechanisms of the SFRP2 gene in porcine skeletal muscle development, we first analyzed the sequence structure of the porcine SFRP2 gene. Subsequently, we detected its tissue distribution in adult Tongcheng pigs （a Chinese indigenous breed） and investigated its dynamic expression in developmental skeletal muscle （13 prenatal and 7 postnatal time points）in Tongcheng pigs. An interaction analysis between SFRP2 and myomiRs was also performed. The results showed that the expression pattern of the SFRP2 varied greatly across diverse tissues. It exhibited abundant expression in prenatal skeletal muscle and peaked at 55 days post coitus （E55）, and had a lower expression in postnatal skeletal muscle, indicating that the SFRP2 gene might affect porcine embryonic skeletal muscle development. Co-expression analysis revealed that the expression levels of SFRP2 correlated negatively with miRNA-1 （t=-0.570, P-value=0.009） and miRNA-206 （r=-0.546, P-value=0.013）, but positively with SFRP1 （r=0.613, P-value=0.004）. The bioinformatics analysis and dual luciferase assay verified that the SFRP2 was a putative target of miRNA-1/206 in pigs. Therefore, this study is helpful for understanding the biological function and mo- lecular regulation of the SFRP2 gene during porcine skeletal muscle development.展开更多
文摘目的:研究SFRPs家族中SFRP1、SFRP2、SFRP4、SFRP5基因启动子区甲基化状况,探讨基因的甲基化与肾透明细胞癌发生发展的关系。方法:采用甲基化特异性PCR(methylation specific PCR,MSP)方法检测66例肾透明细胞癌及30例癌旁组织中SFRP1、SFRP2、SFRP4、SFRP5基因启动子区甲基化状态及其与临床病理学资料之间的关系。结果:肾透明细胞癌组织中SFRP1、SFRP2、SFRP4、SFRP5基因甲基化率分别为77.3%(51/66)、72.7%(48/66)、59.1%(39/66)、69.7%(46/66),均显著高于相应的癌旁组织,结果有统计学意义(P<0.05)。与临床病理学资料相联系,肾透明细胞癌组织中SFRP1、SFRP5基因甲基化与肿瘤TNM分期相关;SFRP4基因甲基化与肿瘤的病理学分级相关(P<0.05)。结论:SFRP1、SFRP2、SFRP4、SFRP5基因的甲基化均可能参与肾透明细胞癌的发生。SFRP1、SFRP5基因甲基化可能与肾透明细胞癌的发展,浸润和转移有关。SFRP4基因甲基化可能与肾透明细胞癌的恶性行为有关。
基金supported by the grant from Programs of Science and Technology Commission Foundation of Jiangsu Province(NO.BS2005036)
文摘Objective：To investigate the feasibility of the combination of detecting hypermethylated secreted frizzled-related protein 1 （SFRP1） and secreted frizzled-related protein 2（SFRP2） in feces as a panel of biomarkers for colorectal cancer（CRC） screening. Methods： Methylation-specific PCR（MSP） was performed to analyze methylation status of SFRP1 and SFRP2 in a blinded fashion in tumor tissues and in matched stool samples from 39 patients with primary CRC, 34 patients with adenomas, 17 patients with hyperplastic polyps and 20 endoscopically normal subjects as normal controls. Simultaneously we analyzed the correlation of hypermethylated SFRP1 and SFRP2 with the clinicopathological features of CRC. Results：Hypermethylated SFRP1 was detected in 92.3%, 76.5%, 47.1% of tissue samples and in 89.7%, 64.7%, 35.3% of matched fecal samples from CRC, adenoma and hyperplastic polyp, respectively. Hypermethylated SFRP2 was detected in 87.2%, 67.6%, 35.3% of tissue samples and in 82.1%, 55.9%, 29.4% of matched fecal samples from CRC, adenoma and hyperplastic polyp, respectively. Of these two genes, at least one hypermethylated was 94.9%, 82.4%, 52.9% in tissue samples and 92.3%,73.5%, 47.1% in matched fecal samples from CRC, adenoma and hyperplastic polyp, respectively. In contrast, no hypermethylated SFRP1 and SFRP2 were detected in mucosa tissues of normal controls, only 2 cases of fecal samples was detected with hypermethylated SFRP1 and another 1 case was detected with hypermethylated SFRP2. Moreover, no significant associations were observed between hypermethylated SFRP1,SFRP2 and clinicopathological features of CRC. Conclusion： Hypermethylation of SFRP1 and SFRP2 in feces are novel epigenetic biomarkers of CRC and carded high potential for the remote detection of CRC as non-invasive screening method, and combined analysis of hypermethylated SFRP1 and SFRP2 in fecal could further increase the detection rate of CRC and premalignant lesions.
基金supported by the National Key Project (2015ZX08009-001)the National Basic Research Program of China (2012CB124706-6)+1 种基金the National Natural Science Foundation of China (31330074, 31171192)the Agricultural Science and Technology Innovation Program, China (ASTIP-IAS05)
文摘Secreted frizzled-related protein 2 （SFRP2）, a member of the SFRPs family, is associated with cell growth and differentiation in myogenesis. Our previous study suggested that SFRP2 was a potential target of microRNA （miRNA）-I/206, which was considered as myomiRs. To further explore the biological function and regulation mechanisms of the SFRP2 gene in porcine skeletal muscle development, we first analyzed the sequence structure of the porcine SFRP2 gene. Subsequently, we detected its tissue distribution in adult Tongcheng pigs （a Chinese indigenous breed） and investigated its dynamic expression in developmental skeletal muscle （13 prenatal and 7 postnatal time points）in Tongcheng pigs. An interaction analysis between SFRP2 and myomiRs was also performed. The results showed that the expression pattern of the SFRP2 varied greatly across diverse tissues. It exhibited abundant expression in prenatal skeletal muscle and peaked at 55 days post coitus （E55）, and had a lower expression in postnatal skeletal muscle, indicating that the SFRP2 gene might affect porcine embryonic skeletal muscle development. Co-expression analysis revealed that the expression levels of SFRP2 correlated negatively with miRNA-1 （t=-0.570, P-value=0.009） and miRNA-206 （r=-0.546, P-value=0.013）, but positively with SFRP1 （r=0.613, P-value=0.004）. The bioinformatics analysis and dual luciferase assay verified that the SFRP2 was a putative target of miRNA-1/206 in pigs. Therefore, this study is helpful for understanding the biological function and mo- lecular regulation of the SFRP2 gene during porcine skeletal muscle development.
