Objective： Colorectal cancer（CRC） is one of the most common types of human cancers. As a tumor suppressor, SMAD4 plays a key role in colorectal carcinogenesis and invasiveness. Copy number variations（CNVs） of the...Objective： Colorectal cancer（CRC） is one of the most common types of human cancers. As a tumor suppressor, SMAD4 plays a key role in colorectal carcinogenesis and invasiveness. Copy number variations（CNVs） of the SMAD4 gene have been reported to be associated with cancer pathogenesis in array-based studies in different populations. Here we aimed to investigate the CNVs of the SMAD4 gene in a relatively large number of CRC patients from China. Methods： In the present study, we collected 147 Chinese CRC tumors as well as self-paired normal control tissues. Quantitative PCR was carried out to examine the copy number as well as the m RNA expression of the SMAD4 gene. Results： Our results showed that the copy number deletions of SMAD4 were frequent in a relatively high percentage of CRC samples（34.7%, 51 out of 147）. There was a positive correlation between the copy number decrease of SMAD4 and tumor progression in CRCs. Furthermore, copy number loss of SMAD4 was correlated with decreased m RNA expression.Conclusions： These findings suggested that the copy number deletions of SMAD4 were frequent in CRC patients from China and had the potential to serve as a diagnostic indicator, alone or in combination with other markers, for CRC.展开更多
目的:探讨贲门腺癌(gastric cardia adenocarcinoma,GCA)中Smad4(mothers against decapentaplegic homolog4)基因启动子区及第1外显子区的甲基化状态及其与TGF-β1蛋白表达之间的相关性。方法:取110例贲门腺癌组织及相应癌旁组织,分别...目的:探讨贲门腺癌(gastric cardia adenocarcinoma,GCA)中Smad4(mothers against decapentaplegic homolog4)基因启动子区及第1外显子区的甲基化状态及其与TGF-β1蛋白表达之间的相关性。方法:取110例贲门腺癌组织及相应癌旁组织,分别采用甲基化特异性PCR(methylation specific PCR,MSP)方法检测Smad4基因的甲基化情况,RT-PCR方法检测Smad4 mRNA水平,免疫组织化学法检测Smad4和TGF-β1的蛋白表达情况。结果:贲门腺癌组织Smad4基因启动子甲基化率为5.5%(6/110),Smad4基因第1外显子5′非翻译区的甲基化率为24.5%(27/110),相应癌旁正常黏膜均未检测到此两个位点的甲基化,癌组Smad4基因甲基化率显著高于癌旁正常组织(P<0.05),且贲门腺癌中Smad4基因5′非翻译区发生甲基化的比率显并高于启动子区(P<0.01)。贲门腺癌组织中Smad4 mRNA及蛋白表达显著低于癌旁正常组织(P<0.05),其甲基化与蛋白表达之间呈负相关。TGF-β1在贲门癌组织中的表达(65.5%)明显高于相应癌旁组织(15.5%)(P<0.01),且随肿瘤分期的增高和肿瘤分化程度的降低,TGF-β1的阳性表达率明显升高(P<0.05)。Smad4蛋白和TGF-β1蛋白在贲门腺癌中的表达呈明显的负相关。结论:在贲门腺癌发生发展过程中Smad4基因第1外显子的5′非翻译区比启动子区更易发生高甲基化而导致基因沉默,Smad4甲基化及TGF-β1的过表达可能是贲门腺癌发生的机制之一。展开更多
基金supported by grants from Scientific Research Foundation of Hubei Health Department (JX3B88)
文摘Objective： Colorectal cancer（CRC） is one of the most common types of human cancers. As a tumor suppressor, SMAD4 plays a key role in colorectal carcinogenesis and invasiveness. Copy number variations（CNVs） of the SMAD4 gene have been reported to be associated with cancer pathogenesis in array-based studies in different populations. Here we aimed to investigate the CNVs of the SMAD4 gene in a relatively large number of CRC patients from China. Methods： In the present study, we collected 147 Chinese CRC tumors as well as self-paired normal control tissues. Quantitative PCR was carried out to examine the copy number as well as the m RNA expression of the SMAD4 gene. Results： Our results showed that the copy number deletions of SMAD4 were frequent in a relatively high percentage of CRC samples（34.7%, 51 out of 147）. There was a positive correlation between the copy number decrease of SMAD4 and tumor progression in CRCs. Furthermore, copy number loss of SMAD4 was correlated with decreased m RNA expression.Conclusions： These findings suggested that the copy number deletions of SMAD4 were frequent in CRC patients from China and had the potential to serve as a diagnostic indicator, alone or in combination with other markers, for CRC.
文摘目的:探讨贲门腺癌(gastric cardia adenocarcinoma,GCA)中Smad4(mothers against decapentaplegic homolog4)基因启动子区及第1外显子区的甲基化状态及其与TGF-β1蛋白表达之间的相关性。方法:取110例贲门腺癌组织及相应癌旁组织,分别采用甲基化特异性PCR(methylation specific PCR,MSP)方法检测Smad4基因的甲基化情况,RT-PCR方法检测Smad4 mRNA水平,免疫组织化学法检测Smad4和TGF-β1的蛋白表达情况。结果:贲门腺癌组织Smad4基因启动子甲基化率为5.5%(6/110),Smad4基因第1外显子5′非翻译区的甲基化率为24.5%(27/110),相应癌旁正常黏膜均未检测到此两个位点的甲基化,癌组Smad4基因甲基化率显著高于癌旁正常组织(P<0.05),且贲门腺癌中Smad4基因5′非翻译区发生甲基化的比率显并高于启动子区(P<0.01)。贲门腺癌组织中Smad4 mRNA及蛋白表达显著低于癌旁正常组织(P<0.05),其甲基化与蛋白表达之间呈负相关。TGF-β1在贲门癌组织中的表达(65.5%)明显高于相应癌旁组织(15.5%)(P<0.01),且随肿瘤分期的增高和肿瘤分化程度的降低,TGF-β1的阳性表达率明显升高(P<0.05)。Smad4蛋白和TGF-β1蛋白在贲门腺癌中的表达呈明显的负相关。结论:在贲门腺癌发生发展过程中Smad4基因第1外显子的5′非翻译区比启动子区更易发生高甲基化而导致基因沉默,Smad4甲基化及TGF-β1的过表达可能是贲门腺癌发生的机制之一。
