目的探讨三阴型乳腺癌(triple-negative breast cancer,TNBC)中FOXC1、SOX10的表达与临床病理特征的关系及其临床意义。方法收集90例TNBC、60例非特殊类型浸润性乳腺癌(invasive breast carcinoma of no special type,IBC-NST)、40例癌...目的探讨三阴型乳腺癌(triple-negative breast cancer,TNBC)中FOXC1、SOX10的表达与临床病理特征的关系及其临床意义。方法收集90例TNBC、60例非特殊类型浸润性乳腺癌(invasive breast carcinoma of no special type,IBC-NST)、40例癌旁正常乳腺组织石蜡标本,采用免疫组化法检测FOXC1、SOX10的表达,分析其与临床病理特征的关系并复习相关文献。结果FOXC1和SOX10在TNBC(82.2%、70.0%)中阳性率均明显高于IBC-NST(11.7%、13.3%)及癌旁正常乳腺组织(7.5%、0),差异有统计学意义。FOXC1表达与TNBC肿瘤最大径、组织学分级、淋巴结转移、Ki-67增殖指数高、预后分期均相关(P<0.05),SOX10表达与TNBC肿瘤最大径、组织学分级、Ki-67增殖指数高、预后分期均相关(P<0.05),且TNBC中FOXC1与SOX10表达呈正相关(R=0.71,P<0.001)。Kaplan-Meier结果示FOXC1与肿瘤无进展生存期相关(P<0.05)。结论FOXC1和SOX10在TNBC中高表达,两者参与TNBC的发生、发展,在侵袭转移中可能起协同作用,对预后判断有一定价值。展开更多
BACKGROUND:A growing body of evidence suggests that many tumors are initiated by both epigenetic abnormalities and gene mutations,which promote tumor progression. Epigenetic abnormalities include changes in DNA methyl...BACKGROUND:A growing body of evidence suggests that many tumors are initiated by both epigenetic abnormalities and gene mutations,which promote tumor progression. Epigenetic abnormalities include changes in DNA methylation and in the modification of histones.This study aimed to assess the status of methylation in the CpG island(CGI)of the tumor necrosis factor receptor superfamily member 10c(TNFRSF10C) with combined bisulfite restriction analysis(COBRA)and to evaluate its role in the progression of pancreatic cancer(PC). METHODS:The methylation status of four PC cell lines was assessed using COBRA and/or bisulfite genomic sequencing (BGS).Changes in methylation and TNFRSF10C expression in PC cell lines before and after treatment with 5-aza-2’-deoxycytidine(5-aza-dC)and/or trichostatin A(TSA)were assessed by BGS and real-time RT-PCR.Apoptosis in the four cell lines was tested by flow cytometry(FCM)and TUNEL assay. RESULTS:The methylation status of the TNFRSF10C promoter was assessed in PC cells(BxPC-3:68.84±8.71%;CFPAC-1:0; PANC-1:96.77±4.57%;SW1990:54.97±7.33%)with the COBRA assay,which was confirmed by the results of BGS.After treatment with 5-aza-dC and/or TSA,apoptosis was induced in PC cells to different degrees,and the levels of TNFRSF10C transcriptional expression in the PC cell lines(except CFPAC-1) increased markedly after 5-aza-dC treatment. CONCLUSIONS:A high frequency of CGI methylation in the TNFRSF10C promoter results in inactivation of the gene and enhancement of tumor growth in most PC cell lines(except CFPAC-1).Inactivation of TNFRSF10C by CGI hypermethylation can play an important role in PC progression and be potentially useful as a diagnostic marker and a new therapeutic approach for PC.展开更多
文摘目的探讨三阴型乳腺癌(triple-negative breast cancer,TNBC)中FOXC1、SOX10的表达与临床病理特征的关系及其临床意义。方法收集90例TNBC、60例非特殊类型浸润性乳腺癌(invasive breast carcinoma of no special type,IBC-NST)、40例癌旁正常乳腺组织石蜡标本,采用免疫组化法检测FOXC1、SOX10的表达,分析其与临床病理特征的关系并复习相关文献。结果FOXC1和SOX10在TNBC(82.2%、70.0%)中阳性率均明显高于IBC-NST(11.7%、13.3%)及癌旁正常乳腺组织(7.5%、0),差异有统计学意义。FOXC1表达与TNBC肿瘤最大径、组织学分级、淋巴结转移、Ki-67增殖指数高、预后分期均相关(P<0.05),SOX10表达与TNBC肿瘤最大径、组织学分级、Ki-67增殖指数高、预后分期均相关(P<0.05),且TNBC中FOXC1与SOX10表达呈正相关(R=0.71,P<0.001)。Kaplan-Meier结果示FOXC1与肿瘤无进展生存期相关(P<0.05)。结论FOXC1和SOX10在TNBC中高表达,两者参与TNBC的发生、发展,在侵袭转移中可能起协同作用,对预后判断有一定价值。
基金supported by a grant from the National Natural Science Foundation of China(30471691)
文摘BACKGROUND:A growing body of evidence suggests that many tumors are initiated by both epigenetic abnormalities and gene mutations,which promote tumor progression. Epigenetic abnormalities include changes in DNA methylation and in the modification of histones.This study aimed to assess the status of methylation in the CpG island(CGI)of the tumor necrosis factor receptor superfamily member 10c(TNFRSF10C) with combined bisulfite restriction analysis(COBRA)and to evaluate its role in the progression of pancreatic cancer(PC). METHODS:The methylation status of four PC cell lines was assessed using COBRA and/or bisulfite genomic sequencing (BGS).Changes in methylation and TNFRSF10C expression in PC cell lines before and after treatment with 5-aza-2’-deoxycytidine(5-aza-dC)and/or trichostatin A(TSA)were assessed by BGS and real-time RT-PCR.Apoptosis in the four cell lines was tested by flow cytometry(FCM)and TUNEL assay. RESULTS:The methylation status of the TNFRSF10C promoter was assessed in PC cells(BxPC-3:68.84±8.71%;CFPAC-1:0; PANC-1:96.77±4.57%;SW1990:54.97±7.33%)with the COBRA assay,which was confirmed by the results of BGS.After treatment with 5-aza-dC and/or TSA,apoptosis was induced in PC cells to different degrees,and the levels of TNFRSF10C transcriptional expression in the PC cell lines(except CFPAC-1) increased markedly after 5-aza-dC treatment. CONCLUSIONS:A high frequency of CGI methylation in the TNFRSF10C promoter results in inactivation of the gene and enhancement of tumor growth in most PC cell lines(except CFPAC-1).Inactivation of TNFRSF10C by CGI hypermethylation can play an important role in PC progression and be potentially useful as a diagnostic marker and a new therapeutic approach for PC.
