Objective:Metastasis is one of the key causes of high mortality in lung cancer.Aberrant DNA methylation is a common event in metastatic lung cancer.We aimed to identify new epigenetic regulation of metastasis-associat...Objective:Metastasis is one of the key causes of high mortality in lung cancer.Aberrant DNA methylation is a common event in metastatic lung cancer.We aimed to identify new epigenetic regulation of metastasis-associated genes and characterize their effects on lung cancer progression.Methods:We screened genes associated with non-small cell lung cancer(NSCLC)metastasis by integrating datasets from the Gene Expression Omnibus(GEO)database.We obtained epigenetic-regulated candidate genes by analyzing the expression profile of demethylation genes.By overlapping analysis,epigenetically modulated metastasis-associated genes were obtained.Kaplan-Meier plotter(KM plotter)was utilized to assess the overall survival(OS)of stomatin in lung cancer.Immunohistochemistry(IHC)was conducted to determine the association between stomatin and metastasis-associated clinical indicators.Both in vitro and in vivo assays were performed to investigate the potential role of stomatin in metastasis.The regulation mechanisms of transforming growth factorβ1(TGFβ1)on stomatin were determined by Sequenom MassARRAY quantitative methylation and western blot assays.Results:A series of bioinformatic analyses revealed stomatin as the metastasis-associated gene regulated by DNA methylation.The KM plotter analysis showed a positive association between stomatin and the OS of lung cancer.IHC analysis indicated that the decreased stomatin expression is linked with advanced TNM stage.Loss-and gainof-function experiments displayed that stomatin could inhibit the migration and invasion of NSCLC cells.Furthermore,TGFβ1 repressed stomatin expression during epithelial-to-mesenchymal transition(EMT).The negative correlation between stomatin and TGFβ1 was also validated in advanced stage III lung tumor samples.The underlying mechanism by which TGFβ1 inhibits stomatin is due in part to DNA methylation.Conclusions:Our results suggest that stomatin may be a target for epigenetic regulation and can be used to prevent metastatic diseases.展开更多
在口腔、食管和结直肠癌病灶中,TATA序列结合蛋白相关因子1(TATA-box binding protein associated factor 1 like,TAF1L)、stomatin家族蛋白1(stomatin-like protein 1,STOML1)和stomatin家族蛋白2(stomatin-like protein 2,STOML2)存...在口腔、食管和结直肠癌病灶中,TATA序列结合蛋白相关因子1(TATA-box binding protein associated factor 1 like,TAF1L)、stomatin家族蛋白1(stomatin-like protein 1,STOML1)和stomatin家族蛋白2(stomatin-like protein 2,STOML2)存在异常表达.为探究它们在消化系统癌变过程中的作用机理,利用6种消化道肿瘤(食道、胃、结肠、直肠、肝脏和胰腺)及癌旁组织的微陈列芯片,通过多重免疫组织化学染色,比对分析TAF1L、STOML1和STOML2这3种蛋白质在癌与癌旁组织的差异表达及与癌变的关联.结果发现,STOML2在食道、胃、结肠、直肠、肝脏和胰腺这6种消化系统癌组织中均呈显著性高表达(P<0.001),而同一家族成员STOML1则仅在食管癌和肝癌组织中表达明显增高(P<0.005).另外,除胰腺癌灶外,TAF1L在其余5种消化系统癌组织中也呈现高表达(P<0.005).同时,TAF1L、STOML1和STOML2这3种蛋白质均与上皮间充质转化的关键蛋白质MMP9有共定位现象.由此表明,3种蛋白质TAF1L、STOML1和STOML2在多种癌组织中可能具有广泛的促癌作用.由于3种蛋白质在多种癌组织的表达水平不同,说明它们各自存在着组织特异性,且具有不同的功能使命,需进一步研究TAF1L、STOML1和STOML2这3种蛋白质在消化系统恶性肿瘤发生发展过程中各自的分子病理学潜能,如能将它们打造成用于精准诊疗和预后判断的新型分子标志物,此研究结果将有重要的临床意义.展开更多
目的:研究stomatin样蛋白2(stomatin-like protein 2,SLP-2)对人子宫内膜基质细胞系T-HESC的增殖和分化的调控作用。方法:培养子宫内膜基质细胞系T-HESC,体外诱导蜕膜化,RT-q PCR、Western blot和免疫荧光方法检测SLP-2在体外诱导蜕膜...目的:研究stomatin样蛋白2(stomatin-like protein 2,SLP-2)对人子宫内膜基质细胞系T-HESC的增殖和分化的调控作用。方法:培养子宫内膜基质细胞系T-HESC,体外诱导蜕膜化,RT-q PCR、Western blot和免疫荧光方法检测SLP-2在体外诱导蜕膜化模型中的表达变化以及蜕膜化标志分子催乳素(prolactin,PRL)、胰岛素样生长因子结合蛋白1(insulin like growth factor binding protein 1,IGFBP1)和Desmin的表达。转染特异性SLP-2干扰小RNA(si RNA),敲低SLP-2的表达,分析敲低SLP-2表达对基质细胞增殖和分化(蜕膜化)的影响。结果:体外诱导蜕膜化条件下,诱导蜕膜化标志物IGFBP1和PRL的表达明显增加;Desmin显著表达于在体外诱导蜕膜化的细胞中;SLP-2表达明显升高。在蜕膜化细胞中转染SLP-2 si RNA敲低SLP-2表达,蜕膜化行为受到显著抑制;细胞增殖标志分子CCND3表达明显下降,细胞增殖降低。结论:SLP-2的表达可影响人子宫内膜基质细胞细胞系T-HESC的增殖和分化。展开更多
目的:探讨红细胞膜整合蛋白SLP-2(stomatin-like protein 2)在胃癌中的表达及其与临床病理学指标及预后的关系。方法:选取中山大学肿瘤防治中心病理科有完整临床资料的胃癌手术标本190例,应用免疫组织化学方法检测胃癌中SLP-2蛋白的表达...目的:探讨红细胞膜整合蛋白SLP-2(stomatin-like protein 2)在胃癌中的表达及其与临床病理学指标及预后的关系。方法:选取中山大学肿瘤防治中心病理科有完整临床资料的胃癌手术标本190例,应用免疫组织化学方法检测胃癌中SLP-2蛋白的表达,并分析其与临床病理特征及预后的关系。结果:(1)胃癌组织中SLP-2蛋白表达的阳性率为63.2%(120/190)。SLP-2表达与胃癌浸润深度、TNM分期及淋巴结转移有关(P<0.05),而与患者性别、年龄、肿瘤分化程度、肿瘤直径和远处转移均无关(P>0.05);(2)Kaplan-Meier生存曲线分析结果显示:SLP-2阳性表达患者的累积生存率明显低于阴性表达患者(P<0.01);(3)单因素分析结果显示:SLP-2的表达、淋巴结转移、肿瘤分化程度、肿瘤直径、TNM分期、浸润深度及远处转移均影响胃癌预后;多因素分析表明,只有肿瘤直径和TNM分期是独立的预后指标。结论:(1)SLP-2在胃腺癌组织中高表达,可能参与胃腺癌的发生发展和转移;(2)SLP-2在一定程度上影响胃癌的预后,其过度表达提示胃癌预后差。展开更多
目的:研究SLP-2(stomatin like protein2)基因在结肠癌及正常结肠黏膜中的表达情况.方法:应用RT-PCR法及免疫组织化学法分别检测40例和50例结肠癌及其癌旁正常结肠黏膜中SLP-2mRNA和蛋白的表达,并结合免疫组织化学结果及结肠癌患者的临...目的:研究SLP-2(stomatin like protein2)基因在结肠癌及正常结肠黏膜中的表达情况.方法:应用RT-PCR法及免疫组织化学法分别检测40例和50例结肠癌及其癌旁正常结肠黏膜中SLP-2mRNA和蛋白的表达,并结合免疫组织化学结果及结肠癌患者的临床病理资料进行分析.结果:RT-PCR结果显示,结肠癌及配对癌旁正常组织中SLP-2mRNA的表达水平分别为1.31±0.28和0.74±0.16,前者较后者明显升高(P<0.05).免疫组织化学结果显示,SLP-2蛋白在结肠癌及配对癌旁正常组织中的高表达率分别为70.0%(35/50)和22%(11/50),两者差异有统计学意义(P<0.05).且SLP-2蛋白的表达与有无淋巴结转移及TNM分期相关(均P<0.05).结论:SLP-2基因在结肠癌组织中高表达,可能参与结肠癌的发生发展和转移.展开更多
基金supported by the National Natural Science Foundation of China (No. 81602576, 81802872)National Key Research and Development Program of China (No. 2016YFA0201503)Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (CIFMS) (No. 2016I2M-1-007, 2018-I2M-1-002)
文摘Objective:Metastasis is one of the key causes of high mortality in lung cancer.Aberrant DNA methylation is a common event in metastatic lung cancer.We aimed to identify new epigenetic regulation of metastasis-associated genes and characterize their effects on lung cancer progression.Methods:We screened genes associated with non-small cell lung cancer(NSCLC)metastasis by integrating datasets from the Gene Expression Omnibus(GEO)database.We obtained epigenetic-regulated candidate genes by analyzing the expression profile of demethylation genes.By overlapping analysis,epigenetically modulated metastasis-associated genes were obtained.Kaplan-Meier plotter(KM plotter)was utilized to assess the overall survival(OS)of stomatin in lung cancer.Immunohistochemistry(IHC)was conducted to determine the association between stomatin and metastasis-associated clinical indicators.Both in vitro and in vivo assays were performed to investigate the potential role of stomatin in metastasis.The regulation mechanisms of transforming growth factorβ1(TGFβ1)on stomatin were determined by Sequenom MassARRAY quantitative methylation and western blot assays.Results:A series of bioinformatic analyses revealed stomatin as the metastasis-associated gene regulated by DNA methylation.The KM plotter analysis showed a positive association between stomatin and the OS of lung cancer.IHC analysis indicated that the decreased stomatin expression is linked with advanced TNM stage.Loss-and gainof-function experiments displayed that stomatin could inhibit the migration and invasion of NSCLC cells.Furthermore,TGFβ1 repressed stomatin expression during epithelial-to-mesenchymal transition(EMT).The negative correlation between stomatin and TGFβ1 was also validated in advanced stage III lung tumor samples.The underlying mechanism by which TGFβ1 inhibits stomatin is due in part to DNA methylation.Conclusions:Our results suggest that stomatin may be a target for epigenetic regulation and can be used to prevent metastatic diseases.
文摘在口腔、食管和结直肠癌病灶中,TATA序列结合蛋白相关因子1(TATA-box binding protein associated factor 1 like,TAF1L)、stomatin家族蛋白1(stomatin-like protein 1,STOML1)和stomatin家族蛋白2(stomatin-like protein 2,STOML2)存在异常表达.为探究它们在消化系统癌变过程中的作用机理,利用6种消化道肿瘤(食道、胃、结肠、直肠、肝脏和胰腺)及癌旁组织的微陈列芯片,通过多重免疫组织化学染色,比对分析TAF1L、STOML1和STOML2这3种蛋白质在癌与癌旁组织的差异表达及与癌变的关联.结果发现,STOML2在食道、胃、结肠、直肠、肝脏和胰腺这6种消化系统癌组织中均呈显著性高表达(P<0.001),而同一家族成员STOML1则仅在食管癌和肝癌组织中表达明显增高(P<0.005).另外,除胰腺癌灶外,TAF1L在其余5种消化系统癌组织中也呈现高表达(P<0.005).同时,TAF1L、STOML1和STOML2这3种蛋白质均与上皮间充质转化的关键蛋白质MMP9有共定位现象.由此表明,3种蛋白质TAF1L、STOML1和STOML2在多种癌组织中可能具有广泛的促癌作用.由于3种蛋白质在多种癌组织的表达水平不同,说明它们各自存在着组织特异性,且具有不同的功能使命,需进一步研究TAF1L、STOML1和STOML2这3种蛋白质在消化系统恶性肿瘤发生发展过程中各自的分子病理学潜能,如能将它们打造成用于精准诊疗和预后判断的新型分子标志物,此研究结果将有重要的临床意义.
文摘目的:研究stomatin样蛋白2(stomatin-like protein 2,SLP-2)对人子宫内膜基质细胞系T-HESC的增殖和分化的调控作用。方法:培养子宫内膜基质细胞系T-HESC,体外诱导蜕膜化,RT-q PCR、Western blot和免疫荧光方法检测SLP-2在体外诱导蜕膜化模型中的表达变化以及蜕膜化标志分子催乳素(prolactin,PRL)、胰岛素样生长因子结合蛋白1(insulin like growth factor binding protein 1,IGFBP1)和Desmin的表达。转染特异性SLP-2干扰小RNA(si RNA),敲低SLP-2的表达,分析敲低SLP-2表达对基质细胞增殖和分化(蜕膜化)的影响。结果:体外诱导蜕膜化条件下,诱导蜕膜化标志物IGFBP1和PRL的表达明显增加;Desmin显著表达于在体外诱导蜕膜化的细胞中;SLP-2表达明显升高。在蜕膜化细胞中转染SLP-2 si RNA敲低SLP-2表达,蜕膜化行为受到显著抑制;细胞增殖标志分子CCND3表达明显下降,细胞增殖降低。结论:SLP-2的表达可影响人子宫内膜基质细胞细胞系T-HESC的增殖和分化。
文摘目的:探讨红细胞膜整合蛋白SLP-2(stomatin-like protein 2)在胃癌中的表达及其与临床病理学指标及预后的关系。方法:选取中山大学肿瘤防治中心病理科有完整临床资料的胃癌手术标本190例,应用免疫组织化学方法检测胃癌中SLP-2蛋白的表达,并分析其与临床病理特征及预后的关系。结果:(1)胃癌组织中SLP-2蛋白表达的阳性率为63.2%(120/190)。SLP-2表达与胃癌浸润深度、TNM分期及淋巴结转移有关(P<0.05),而与患者性别、年龄、肿瘤分化程度、肿瘤直径和远处转移均无关(P>0.05);(2)Kaplan-Meier生存曲线分析结果显示:SLP-2阳性表达患者的累积生存率明显低于阴性表达患者(P<0.01);(3)单因素分析结果显示:SLP-2的表达、淋巴结转移、肿瘤分化程度、肿瘤直径、TNM分期、浸润深度及远处转移均影响胃癌预后;多因素分析表明,只有肿瘤直径和TNM分期是独立的预后指标。结论:(1)SLP-2在胃腺癌组织中高表达,可能参与胃腺癌的发生发展和转移;(2)SLP-2在一定程度上影响胃癌的预后,其过度表达提示胃癌预后差。
文摘目的:研究SLP-2(stomatin like protein2)基因在结肠癌及正常结肠黏膜中的表达情况.方法:应用RT-PCR法及免疫组织化学法分别检测40例和50例结肠癌及其癌旁正常结肠黏膜中SLP-2mRNA和蛋白的表达,并结合免疫组织化学结果及结肠癌患者的临床病理资料进行分析.结果:RT-PCR结果显示,结肠癌及配对癌旁正常组织中SLP-2mRNA的表达水平分别为1.31±0.28和0.74±0.16,前者较后者明显升高(P<0.05).免疫组织化学结果显示,SLP-2蛋白在结肠癌及配对癌旁正常组织中的高表达率分别为70.0%(35/50)和22%(11/50),两者差异有统计学意义(P<0.05).且SLP-2蛋白的表达与有无淋巴结转移及TNM分期相关(均P<0.05).结论:SLP-2基因在结肠癌组织中高表达,可能参与结肠癌的发生发展和转移.
