人类自然杀伤细胞活化性配体UL16结合蛋白(UL16-binding proteins,ULBPs)家族至少由6个成员组成,其中ULBP1、ULBP2、ULBP3(ULl6-binding protein 1-3)分子含有α1和α2结构域,通过糖基磷脂酰肌醇(giycosylphosphatidylinositol,GPI)与...人类自然杀伤细胞活化性配体UL16结合蛋白(UL16-binding proteins,ULBPs)家族至少由6个成员组成,其中ULBP1、ULBP2、ULBP3(ULl6-binding protein 1-3)分子含有α1和α2结构域,通过糖基磷脂酰肌醇(giycosylphosphatidylinositol,GPI)与细胞膜相连。ULBP4(UL16-binding protein 4)分子含有跨膜和胞质结构域。正常组织中广泛表达ULBPs。T淋巴细胞瘤、结肠癌、卵巢癌等肿瘤细胞表面也有ULBPs的高表达。化学药物、细胞因子、细菌和病毒感染等众多因素都可以调控ULBPs的表达,其中紫外线辐射、化疗药物等诱发的DNA损伤反应可以活化3-磷脂酰肌醇激酶家族类成员(ataxia-telangiecta- sia mutated,ATM)或(ataxia-telangiectasia and Rad3-related,ATR)激酶,进一步活化下游的Chk1、Chk2节点激酶和其他的凋亡相关分子,从而诱导ULBPs的表达,引起肿瘤细胞的生长周期停滞,诱导细胞凋亡,发挥抗肿瘤作用。另外,ULBP1启动子中CRE1位点活化也是上调ULBP1转录和表达的关键因素。对ULBPs表达与调控因素的深入探讨将为阐明肿瘤逃逸机制、寻求抗肿瘤有效药物提供新的作用靶点和思路。展开更多
BACKGROUND Early diagnosis of colorectal cancer(CRC)is of great significance to improve the survival rate and quality of life of patients,but early diagnosis of CRC requires more sensitive techniques.Peripheral blood ...BACKGROUND Early diagnosis of colorectal cancer(CRC)is of great significance to improve the survival rate and quality of life of patients,but early diagnosis of CRC requires more sensitive techniques.Peripheral blood UL16-binding protein 2(ULBP2)and human fibrinogen degradation products(DR-70)are the main indicators for the diagnosis of malignant tumors.AIM To assess ULBP2 and DR-70 potential for the early diagnosis and prognostic evaluation of CRC to provide a reference.METHODS This study involved 60 patients with early-stage CRC(CRC group),50 patients with benign colorectal tumors(benign group),and 50 healthy patients(control group)enrolled at the Affiliated Hospital of Jiangnan University and Jiangsu Province Official Hospital between January,2020 and January,2022.ULBP2 and DR-70 levels in the blood were determined and differences among the three groups and early diagnostic values for CRC were determined.Patients with CRC were divided into the good prognosis and poor prognosis groups,and ULBP2 and DR-70 levels in the blood and diagnostic values were compared.RESULTS ULBP2 and DR-70 serum levels were significantly higher in the CRC group than in the control and benign groups(P<0.05);however,no significant differences were observed between the benign and control groups(P>0.05).Among the 60 patients with CRC followed up for two years,two died(3.33%)and 15 exhibited tumor metastasis,progression,or recurrence(25.00%).ULBP2 and DR-70 serum levels were significantly higher in the poor prognosis group than in the good prognosis group(P<0.05).A receiver operating characteristic curve was plotted.Area under the curve,sensitivity,and specificity of serum ULBP2 with DR-70 for the early diagnosis of CRC were higher than those of the single serum indices(P<0.05)in both the good and poor prognosis groups.CONCLUSION ULBP2 and DR-70 serum levels were significantly high in patients with early-stage CRC.They improved the diagnostic rate of early-stage CRC and predicted patient prognosis,thereby showing clinical application potential.展开更多
目的利用Oncomine、TCGA(The Cancer Genome Atlas)等公共数据库,分析UL16结合蛋白2(ULBP2)基因在结直肠癌中的表达及临床意义。方法通过Oncomine数据库检索关于ULBP2基因转录组mRNA信息,分析ULBP2在不同类型肿瘤中的表达情况;TCGA数据...目的利用Oncomine、TCGA(The Cancer Genome Atlas)等公共数据库,分析UL16结合蛋白2(ULBP2)基因在结直肠癌中的表达及临床意义。方法通过Oncomine数据库检索关于ULBP2基因转录组mRNA信息,分析ULBP2在不同类型肿瘤中的表达情况;TCGA数据库分析ULBP2基因与结直肠癌的预后关系;利用String数据库分析ULBP2与上下游蛋白的相互作用及功能富集分析。结果 Oncomine数据库中共有352项关于ULBP2基因的研究结果,其中有统计学差异的结果有23项,涉及到结直肠癌和结直肠正常组织的研究数据集共有10项,其中结直肠癌组织中ULBP2基因的表达显著高于结直肠正常组织(P<0.05);对TCGA数据库结直肠癌数据进行生存分析,结果表明在结直肠癌患者中ULBP2基因高表达组的生存率明显低于低表达组(P<0.05)。结论大数据分析结果表明,ULBP2基因在结直肠癌组织中呈现高表达,并与患者的预后相关,可能作为其潜在的治疗靶点。展开更多
基金国家自然科学基金(No.3037130230471527)+7 种基金山东省优秀中青年科学家科研奖励基金(No.2005BS03015)中国博士后基金(No.20060390309)山东省博士后基金(No.200603071)Supported by the National Natural Science Foundation of China(No.3037130230471527)the Distinguished Young Scientists Foundation of Shandong Province(No.2005BS03015)the National Postdoctoral Research Foundation of China(No.20060390309)the Postdoctoral Research Foundatioa of Shandong Province(No.200603071)
文摘人类自然杀伤细胞活化性配体UL16结合蛋白(UL16-binding proteins,ULBPs)家族至少由6个成员组成,其中ULBP1、ULBP2、ULBP3(ULl6-binding protein 1-3)分子含有α1和α2结构域,通过糖基磷脂酰肌醇(giycosylphosphatidylinositol,GPI)与细胞膜相连。ULBP4(UL16-binding protein 4)分子含有跨膜和胞质结构域。正常组织中广泛表达ULBPs。T淋巴细胞瘤、结肠癌、卵巢癌等肿瘤细胞表面也有ULBPs的高表达。化学药物、细胞因子、细菌和病毒感染等众多因素都可以调控ULBPs的表达,其中紫外线辐射、化疗药物等诱发的DNA损伤反应可以活化3-磷脂酰肌醇激酶家族类成员(ataxia-telangiecta- sia mutated,ATM)或(ataxia-telangiectasia and Rad3-related,ATR)激酶,进一步活化下游的Chk1、Chk2节点激酶和其他的凋亡相关分子,从而诱导ULBPs的表达,引起肿瘤细胞的生长周期停滞,诱导细胞凋亡,发挥抗肿瘤作用。另外,ULBP1启动子中CRE1位点活化也是上调ULBP1转录和表达的关键因素。对ULBPs表达与调控因素的深入探讨将为阐明肿瘤逃逸机制、寻求抗肿瘤有效药物提供新的作用靶点和思路。
文摘BACKGROUND Early diagnosis of colorectal cancer(CRC)is of great significance to improve the survival rate and quality of life of patients,but early diagnosis of CRC requires more sensitive techniques.Peripheral blood UL16-binding protein 2(ULBP2)and human fibrinogen degradation products(DR-70)are the main indicators for the diagnosis of malignant tumors.AIM To assess ULBP2 and DR-70 potential for the early diagnosis and prognostic evaluation of CRC to provide a reference.METHODS This study involved 60 patients with early-stage CRC(CRC group),50 patients with benign colorectal tumors(benign group),and 50 healthy patients(control group)enrolled at the Affiliated Hospital of Jiangnan University and Jiangsu Province Official Hospital between January,2020 and January,2022.ULBP2 and DR-70 levels in the blood were determined and differences among the three groups and early diagnostic values for CRC were determined.Patients with CRC were divided into the good prognosis and poor prognosis groups,and ULBP2 and DR-70 levels in the blood and diagnostic values were compared.RESULTS ULBP2 and DR-70 serum levels were significantly higher in the CRC group than in the control and benign groups(P<0.05);however,no significant differences were observed between the benign and control groups(P>0.05).Among the 60 patients with CRC followed up for two years,two died(3.33%)and 15 exhibited tumor metastasis,progression,or recurrence(25.00%).ULBP2 and DR-70 serum levels were significantly higher in the poor prognosis group than in the good prognosis group(P<0.05).A receiver operating characteristic curve was plotted.Area under the curve,sensitivity,and specificity of serum ULBP2 with DR-70 for the early diagnosis of CRC were higher than those of the single serum indices(P<0.05)in both the good and poor prognosis groups.CONCLUSION ULBP2 and DR-70 serum levels were significantly high in patients with early-stage CRC.They improved the diagnostic rate of early-stage CRC and predicted patient prognosis,thereby showing clinical application potential.
文摘目的利用Oncomine、TCGA(The Cancer Genome Atlas)等公共数据库,分析UL16结合蛋白2(ULBP2)基因在结直肠癌中的表达及临床意义。方法通过Oncomine数据库检索关于ULBP2基因转录组mRNA信息,分析ULBP2在不同类型肿瘤中的表达情况;TCGA数据库分析ULBP2基因与结直肠癌的预后关系;利用String数据库分析ULBP2与上下游蛋白的相互作用及功能富集分析。结果 Oncomine数据库中共有352项关于ULBP2基因的研究结果,其中有统计学差异的结果有23项,涉及到结直肠癌和结直肠正常组织的研究数据集共有10项,其中结直肠癌组织中ULBP2基因的表达显著高于结直肠正常组织(P<0.05);对TCGA数据库结直肠癌数据进行生存分析,结果表明在结直肠癌患者中ULBP2基因高表达组的生存率明显低于低表达组(P<0.05)。结论大数据分析结果表明,ULBP2基因在结直肠癌组织中呈现高表达,并与患者的预后相关,可能作为其潜在的治疗靶点。
