目的:探讨Zw10结合因子-1(zeste white 10 interactor-1,Zwint-1)及其变异体(Zwint-1v)在HeLa细胞不同细胞周期中的亚定位。方法:采用胸腺嘧啶核苷双阻断法将HeLa细胞同步化,通过瞬时转染及间接免疫荧光检测,观察Zwint-1及Zwint-1v在HeL...目的:探讨Zw10结合因子-1(zeste white 10 interactor-1,Zwint-1)及其变异体(Zwint-1v)在HeLa细胞不同细胞周期中的亚定位。方法:采用胸腺嘧啶核苷双阻断法将HeLa细胞同步化,通过瞬时转染及间接免疫荧光检测,观察Zwint-1及Zwint-1v在HeLa细胞不同细胞周期中的亚定位。结果:在HeLa细胞间期,Zwint-1野生型定位于细胞质,而Zwint-1v定位于细胞核;在分裂期,Zwint-1野生型及Zwint-1v定位于纺锤体与着丝粒上。Zwint-1v定化较野生型更趋近于细胞核。结论:Zwint-1及Zwint-1v在HeLa细胞不同细胞周期的亚定位存在差异。展开更多
目的探讨Zeste white 10(ZW10)相互作用着丝粒蛋白1(ZW10-interacting kinetochore protein 1,Zwint-1),在头颈部鳞状细胞癌(head and neck squamous cell carcinoma,HNSCC)肿瘤组织中的蛋白表达情况,以及其与临床病理特征之间的关系。...目的探讨Zeste white 10(ZW10)相互作用着丝粒蛋白1(ZW10-interacting kinetochore protein 1,Zwint-1),在头颈部鳞状细胞癌(head and neck squamous cell carcinoma,HNSCC)肿瘤组织中的蛋白表达情况,以及其与临床病理特征之间的关系。方法采用免疫组织化学检测的方法,对16例HNSCC患者的肿瘤组织样本,以及7例相应的癌旁正常组织样本中Zwint-1蛋白进行检测。同时,分析HNSCC相关组织芯片中Zwint-1蛋白表达与HNSCC临床特征的相关性。结果临床样本与组织芯片的检测结果显示,Zwint-1蛋白在HNSCC肿瘤组织中的蛋白表达高于正常组织,其差异具有统计学意义(t=2.399,P<0.05)。组织芯片的检测结果显示,Zwint-1蛋白表达量与HNSCC患者的肿瘤大小(F=2.889,P<0.05)、淋巴结转移(t=2.110,P<0.05)、分化(F=3.667,P<0.05)以及临床分期(F=2.864,P<0.05)均具有相关性。但是卡方检验结果显示,Zwint-1蛋白阳性表达与肿瘤大小(χ^2=3.236,P>0.05)、淋巴结转移(χ^2=1.463,P>0.05)、分化(χ^2=1.271,P>0.05)、临床分期(χ^2=4.179,P>0.05),差异无统计学意义。结论Zwint-1蛋白在HNSCC的发生发展过程中发挥有重要作用,可能是HNSCC潜在的靶向治疗目标。展开更多
目的:探讨Zw10结合因子(Zeste White 10 interactor,Zwint)在食管癌组织中的表达情况及其与临床病理指标的关系和预后的意义。方法:利用免疫组织化学方法检测115例食管癌组织及配对癌旁组织Zwint蛋白的表达,并分析其与临床病理指标的关...目的:探讨Zw10结合因子(Zeste White 10 interactor,Zwint)在食管癌组织中的表达情况及其与临床病理指标的关系和预后的意义。方法:利用免疫组织化学方法检测115例食管癌组织及配对癌旁组织Zwint蛋白的表达,并分析其与临床病理指标的关系及对患者预后的影响。结果:在食管癌组织中,Zwint蛋白阳性87例(76%);配对癌旁组织中,Zwint蛋白阳性44例(38.2%),Zwint在食管癌组织的阳性表达率明显高于配对癌旁组织,差异有统计学意义(χ^(2)=4.452,P=0.041)。Zwint蛋白表达与患者年龄、性别之间的差异无统计学意义(均P>0.05);Zwint蛋白在组织低分化、III期及有淋巴结转移的食管癌组织中阳性表达率明显高于组织中+高分化、I+II期及无淋巴结转移的食管癌组织(χ^(2)=4.103,P=0.047;χ^(2)=4.979,P=0.030;χ^(2)=6.634,P=0.017)。生存分析结果显示:Zwint蛋白阳性表达患者的总生存期(overall-survival,OS)明显差于Zwint蛋白阴性表达者,差异有统计学意义(χ^(2)=8.093,P=0.004)。结论:在食管癌组织中Zwint蛋白阳性表达与组织分化、TNM分期及淋巴结转移相关,并与患者不良预后相关,Zwint可作为食管癌患者预后预测的指标及潜在的治疗靶点。展开更多
Objective ZW10 interacting kinetochore protein(ZWINT)has been demonstrated to play a pivotal role in the growth,invasion,and migration of cancers.Nevertheless,whether the expression levels of ZWINT are significantly c...Objective ZW10 interacting kinetochore protein(ZWINT)has been demonstrated to play a pivotal role in the growth,invasion,and migration of cancers.Nevertheless,whether the expression levels of ZWINT are significantly correlated with clinicopathological characteristics and prognostic outcomes of patients with breast cancer remains elusive.This study systematically investigated the clinical significance of ZWINT expression in breast cancer through integrated molecular subtyping and survival analysis.Methods We systematically characterized the spatial expression pattern of ZWINT across various breast cancer subtypes and assessed its prognostic significance using an integrated bioinformatics approach that involved multi-omics analysis.The approach included the Breast Cancer Gene-Expression Miner v5.1(bc-GenExMiner v5.1),TNMplot,MuTarget,PrognoScan database,and Database for Annotation,Visualization,and Integrated Discovery(DAVID).Results Our analysis revealed consistent upregulation of ZWINT mRNA and protein expression across distinct clinicopathological subtypes of breast cancer.ZWINT overexpression demonstrated significant co-occurrence with truncating mutations in cadherin 1(CDH1)and tumor protein p53(TP53),suggesting potential functional crosstalk in tumor progression pathways.The overexpression of ZWINT correlated with adverse clinical outcomes,showing 48%increased mortality risk(overall survival:HR 1.48,95%CI 1.23–1.79),66%higher recurrence probability(relapse-free survival:1.66,95%CI 1.50–1.84),and 63%elevated metastasis risk(distant metastasis-free survival:HR 1.63,95%CI 1.39–1.90).Multivariate Cox regression incorporating TNM staging and molecular subtypes confirmed ZWINT as an independent prognostic determinant(P<0.001,Harrell’s C-index=0.7827),which was validated through bootstrap resampling(1000 iterations).Conclusion ZWINT may serve as a potential biomarker for prognosis and a possible therapeutic target alongside TP53/CDH1 in breast cancer.展开更多
目的Zw10结合因子(Zeste white 10interactor,Zwint)在多种恶性肿瘤中高表达并与预后不良相关,但在三阴性乳腺癌(triple-negative breast cancer,TNBC)中Zwint的预后价值尚不明确。本研究旨在探讨TNBC中Zwint的表达情况及与预后的关系...目的Zw10结合因子(Zeste white 10interactor,Zwint)在多种恶性肿瘤中高表达并与预后不良相关,但在三阴性乳腺癌(triple-negative breast cancer,TNBC)中Zwint的预后价值尚不明确。本研究旨在探讨TNBC中Zwint的表达情况及与预后的关系。方法选取2009-01-01-2013-01-01湖北医药学院附属东风医院110例TNBC患者的完整临床及病理资料。采用免疫组织化学SP法检测Zwint在TNBC组织及配对癌旁乳腺组织中的表达情况,计算细胞染色强度和阳性细胞所占比例的积分,<4为Zwint低表达组,≥4为Zwint高表达组。应用Kaplan-Meier方法及Cox模型方法分析其与TNBC临床病例特征关系及预后的意义。结果Zwint在TNBC组织的表达56.3%(62/110)高于配对癌旁乳腺组织30%(33/110),差异有统计学意义,χ^2=4.091,P=0.014;Zwint高表达与患者年龄(χ^2=2.471,P=0.116)、化疗方案(χ^2=1.349,P=0.245)、手术方式(χ^2=2.848,P=0.092)差异无统计学意义,与组织学分级(χ^2=7.990,P=0.005)、临床分期(χ^2=4.578,P=0.032)、腋窝淋巴结转移(χ^2=6.914,P=0.009)、Ki-67(χ^2=7.990,P=0.005)差异有统计学意义;随访期间,Zwint高表达组,复发、转移12例,死亡11例,Zwint低表达组,复发、转移4例,死亡4例。Kaplan-Meier生存分析显示,Zwint高表达组的中位OS为75.516(95%CI:71.199~80.853)个月,Zwint低表达组为78.545(95%CI:76.238~82.834)个月,χ^2=6.361,P=0.012;Zwint高表达组的中位DFS为63.170(95%CI:57.043~69.296)个月,Zwint低表达组为78.019(95%CI:75.548~80.489),χ^2=5.321,P=0.021。单因素Cox模型分析显示,Zwint高表达(HR=0.283,95%CI:0.090~0.892,P=0.031)、临床分期Ⅲ期(HR=0.510,95%CI:0.089~0.804,P=0.042)、组织学分级Ⅲ级(HR=1.546,95%CI:1.031~3.354,P=0.037)、腋窝淋巴结转移(HR=0.335,95%CI:0.121~0.924,P=0.035)、Ki-67高表达(HR=0.508,95%CI:0.184~0.974,P=0.025)与TNBC的预后相关,均为预后的危险因素。多因素Cox模型分析显示,Zwint高表达(HR=0.177,95%CI:0.051~0.615,P=0.006)及腋窝淋巴结转移(HR=0.174,95%CI:0.058~0.520,P=0.002)是影响患者预后的独立因素。结论Zwint高表达与TNBC患者预后相关,Zwint高表达患者预后不良,Zwint可作为TNBC患者预后预测指标及潜在治疗靶点。展开更多
文摘目的:探讨Zw10结合因子-1(zeste white 10 interactor-1,Zwint-1)及其变异体(Zwint-1v)在HeLa细胞不同细胞周期中的亚定位。方法:采用胸腺嘧啶核苷双阻断法将HeLa细胞同步化,通过瞬时转染及间接免疫荧光检测,观察Zwint-1及Zwint-1v在HeLa细胞不同细胞周期中的亚定位。结果:在HeLa细胞间期,Zwint-1野生型定位于细胞质,而Zwint-1v定位于细胞核;在分裂期,Zwint-1野生型及Zwint-1v定位于纺锤体与着丝粒上。Zwint-1v定化较野生型更趋近于细胞核。结论:Zwint-1及Zwint-1v在HeLa细胞不同细胞周期的亚定位存在差异。
文摘目的探讨Zeste white 10(ZW10)相互作用着丝粒蛋白1(ZW10-interacting kinetochore protein 1,Zwint-1),在头颈部鳞状细胞癌(head and neck squamous cell carcinoma,HNSCC)肿瘤组织中的蛋白表达情况,以及其与临床病理特征之间的关系。方法采用免疫组织化学检测的方法,对16例HNSCC患者的肿瘤组织样本,以及7例相应的癌旁正常组织样本中Zwint-1蛋白进行检测。同时,分析HNSCC相关组织芯片中Zwint-1蛋白表达与HNSCC临床特征的相关性。结果临床样本与组织芯片的检测结果显示,Zwint-1蛋白在HNSCC肿瘤组织中的蛋白表达高于正常组织,其差异具有统计学意义(t=2.399,P<0.05)。组织芯片的检测结果显示,Zwint-1蛋白表达量与HNSCC患者的肿瘤大小(F=2.889,P<0.05)、淋巴结转移(t=2.110,P<0.05)、分化(F=3.667,P<0.05)以及临床分期(F=2.864,P<0.05)均具有相关性。但是卡方检验结果显示,Zwint-1蛋白阳性表达与肿瘤大小(χ^2=3.236,P>0.05)、淋巴结转移(χ^2=1.463,P>0.05)、分化(χ^2=1.271,P>0.05)、临床分期(χ^2=4.179,P>0.05),差异无统计学意义。结论Zwint-1蛋白在HNSCC的发生发展过程中发挥有重要作用,可能是HNSCC潜在的靶向治疗目标。
文摘目的:探讨Zw10结合因子(Zeste White 10 interactor,Zwint)在食管癌组织中的表达情况及其与临床病理指标的关系和预后的意义。方法:利用免疫组织化学方法检测115例食管癌组织及配对癌旁组织Zwint蛋白的表达,并分析其与临床病理指标的关系及对患者预后的影响。结果:在食管癌组织中,Zwint蛋白阳性87例(76%);配对癌旁组织中,Zwint蛋白阳性44例(38.2%),Zwint在食管癌组织的阳性表达率明显高于配对癌旁组织,差异有统计学意义(χ^(2)=4.452,P=0.041)。Zwint蛋白表达与患者年龄、性别之间的差异无统计学意义(均P>0.05);Zwint蛋白在组织低分化、III期及有淋巴结转移的食管癌组织中阳性表达率明显高于组织中+高分化、I+II期及无淋巴结转移的食管癌组织(χ^(2)=4.103,P=0.047;χ^(2)=4.979,P=0.030;χ^(2)=6.634,P=0.017)。生存分析结果显示:Zwint蛋白阳性表达患者的总生存期(overall-survival,OS)明显差于Zwint蛋白阴性表达者,差异有统计学意义(χ^(2)=8.093,P=0.004)。结论:在食管癌组织中Zwint蛋白阳性表达与组织分化、TNM分期及淋巴结转移相关,并与患者不良预后相关,Zwint可作为食管癌患者预后预测的指标及潜在的治疗靶点。
基金supported by the Research Project of Maternal and Child Health Hospital of Hubei Province(No.2023SFYM008)Key Project of Hubei Provincial Natural Science Foundation(No.JCZRLH202500304).
文摘Objective ZW10 interacting kinetochore protein(ZWINT)has been demonstrated to play a pivotal role in the growth,invasion,and migration of cancers.Nevertheless,whether the expression levels of ZWINT are significantly correlated with clinicopathological characteristics and prognostic outcomes of patients with breast cancer remains elusive.This study systematically investigated the clinical significance of ZWINT expression in breast cancer through integrated molecular subtyping and survival analysis.Methods We systematically characterized the spatial expression pattern of ZWINT across various breast cancer subtypes and assessed its prognostic significance using an integrated bioinformatics approach that involved multi-omics analysis.The approach included the Breast Cancer Gene-Expression Miner v5.1(bc-GenExMiner v5.1),TNMplot,MuTarget,PrognoScan database,and Database for Annotation,Visualization,and Integrated Discovery(DAVID).Results Our analysis revealed consistent upregulation of ZWINT mRNA and protein expression across distinct clinicopathological subtypes of breast cancer.ZWINT overexpression demonstrated significant co-occurrence with truncating mutations in cadherin 1(CDH1)and tumor protein p53(TP53),suggesting potential functional crosstalk in tumor progression pathways.The overexpression of ZWINT correlated with adverse clinical outcomes,showing 48%increased mortality risk(overall survival:HR 1.48,95%CI 1.23–1.79),66%higher recurrence probability(relapse-free survival:1.66,95%CI 1.50–1.84),and 63%elevated metastasis risk(distant metastasis-free survival:HR 1.63,95%CI 1.39–1.90).Multivariate Cox regression incorporating TNM staging and molecular subtypes confirmed ZWINT as an independent prognostic determinant(P<0.001,Harrell’s C-index=0.7827),which was validated through bootstrap resampling(1000 iterations).Conclusion ZWINT may serve as a potential biomarker for prognosis and a possible therapeutic target alongside TP53/CDH1 in breast cancer.
文摘目的Zw10结合因子(Zeste white 10interactor,Zwint)在多种恶性肿瘤中高表达并与预后不良相关,但在三阴性乳腺癌(triple-negative breast cancer,TNBC)中Zwint的预后价值尚不明确。本研究旨在探讨TNBC中Zwint的表达情况及与预后的关系。方法选取2009-01-01-2013-01-01湖北医药学院附属东风医院110例TNBC患者的完整临床及病理资料。采用免疫组织化学SP法检测Zwint在TNBC组织及配对癌旁乳腺组织中的表达情况,计算细胞染色强度和阳性细胞所占比例的积分,<4为Zwint低表达组,≥4为Zwint高表达组。应用Kaplan-Meier方法及Cox模型方法分析其与TNBC临床病例特征关系及预后的意义。结果Zwint在TNBC组织的表达56.3%(62/110)高于配对癌旁乳腺组织30%(33/110),差异有统计学意义,χ^2=4.091,P=0.014;Zwint高表达与患者年龄(χ^2=2.471,P=0.116)、化疗方案(χ^2=1.349,P=0.245)、手术方式(χ^2=2.848,P=0.092)差异无统计学意义,与组织学分级(χ^2=7.990,P=0.005)、临床分期(χ^2=4.578,P=0.032)、腋窝淋巴结转移(χ^2=6.914,P=0.009)、Ki-67(χ^2=7.990,P=0.005)差异有统计学意义;随访期间,Zwint高表达组,复发、转移12例,死亡11例,Zwint低表达组,复发、转移4例,死亡4例。Kaplan-Meier生存分析显示,Zwint高表达组的中位OS为75.516(95%CI:71.199~80.853)个月,Zwint低表达组为78.545(95%CI:76.238~82.834)个月,χ^2=6.361,P=0.012;Zwint高表达组的中位DFS为63.170(95%CI:57.043~69.296)个月,Zwint低表达组为78.019(95%CI:75.548~80.489),χ^2=5.321,P=0.021。单因素Cox模型分析显示,Zwint高表达(HR=0.283,95%CI:0.090~0.892,P=0.031)、临床分期Ⅲ期(HR=0.510,95%CI:0.089~0.804,P=0.042)、组织学分级Ⅲ级(HR=1.546,95%CI:1.031~3.354,P=0.037)、腋窝淋巴结转移(HR=0.335,95%CI:0.121~0.924,P=0.035)、Ki-67高表达(HR=0.508,95%CI:0.184~0.974,P=0.025)与TNBC的预后相关,均为预后的危险因素。多因素Cox模型分析显示,Zwint高表达(HR=0.177,95%CI:0.051~0.615,P=0.006)及腋窝淋巴结转移(HR=0.174,95%CI:0.058~0.520,P=0.002)是影响患者预后的独立因素。结论Zwint高表达与TNBC患者预后相关,Zwint高表达患者预后不良,Zwint可作为TNBC患者预后预测指标及潜在治疗靶点。
