BACKGROUND The prognostic assessment of patients after surgical resection of gastric cancer(GC)patients is critical.However,the role of the circadian clock gene NPAS2 expression in GC remains unknown.AIM To explore th...BACKGROUND The prognostic assessment of patients after surgical resection of gastric cancer(GC)patients is critical.However,the role of the circadian clock gene NPAS2 expression in GC remains unknown.AIM To explore the relationship between NPAS2 and the survival prognosis of GC patients and clarify its role in evaluating GC prognosis.METHODS The tumor tissues and clinical data of 101 patients with GC were collected retrospectively.Immunohistochemical staining(IHC)was used to detect the expression of NPAS2 protein in GC and adjacent tissues.Univariate and multivariate Cox regression analysis was used to determine the independent prognostic factors of GC,and a nomogram prediction model was established.The receiver operating characteristic(ROC)curve,the ROC area under the curve,the calibration curve,and C-index were used to evaluate the predictive effectiveness of the model.Kaplan Meier analysis was used to compare the risk stratification of subgroups according to the median score in the nomogram model of each patient.RESULTS Microarray IHC analysis showed that the positive rate of NPAS2 protein expression in GC tissues was 65.35%,which was significantly higher than 30.69%in adjacent tissues.The high expression of NPAS2 was correlated with tumor-node-metastasis(TNM)stage(P<0.05),pN stage(P<0.05),metastasis(P<0.05),venous invasion(P<0.05),lymphatic invasion(P<0.05),and lymph node positive(P<0.05)of GC.Kaplan Meier survival analysis showed that the 3-year overall survival(OS)of patients with high NPAS2 expression was significantly shortened(P<0.0001).Univariate and multivariate COX regression analysis showed that TNM stage(P=0.009),metastasis(P=0.009),and NPAS2 expression(P=0.020)were independent prognostic factors of OS in GC patients for 3 years.The nomogram prediction model based on independent prognostic factors has a C-Index of 0.740(95%CI:0.713-0.767).Furthermore,subgroup analysis showed that the 3-year OS time of the high-risk group was significantly lower than that of the low-risk group(P<0.0001).CONCLUSION NPAS2 is highly expressed in GC tissues and is closely related to worse OS in patients.Therefore,the evaluation of NPAS2 expression may be a potential marker for GC prognosis evaluation.Notably,the nomogram model based on NPAS2 can improve the accuracy of GC prognosis prediction and assist clinicians in postoperative patient management and decision-making.展开更多
目的检测生物节律基因NPAS2在结直肠癌组织及相应癌旁组织中的表达情况;明确NPAS2的表达与患者临床病理学参数之间的相关性,分析NPAS2表达与结直肠癌患者5年生存率之间的相关性,明确其在判断结直肠癌患者预后中的作用。方法采用RT-q PC...目的检测生物节律基因NPAS2在结直肠癌组织及相应癌旁组织中的表达情况;明确NPAS2的表达与患者临床病理学参数之间的相关性,分析NPAS2表达与结直肠癌患者5年生存率之间的相关性,明确其在判断结直肠癌患者预后中的作用。方法采用RT-q PCR检测NPAS2 m RNA在40例结直肠癌及癌旁新鲜组织中的表达;采用免疫组织化学SABC法检测NPAS2蛋白在120例肿瘤及癌旁石蜡标本中的表达;利用其中78例随访患者资料,K-M生存法分析NPAS2蛋白表达水平与患者生存率之间的相关性。结果 RT-q PCR结果提示,结直肠癌中NPAS2 m RNA表达显著低于相对应的癌旁组织(P<0.01);免疫组织化学结果提示,NPAS2蛋白表达在结直肠癌组织中的阳性率为19.2%,显著低于癌旁中的62.5%(P<0.05)。NPAS2的低表达与结直肠癌的肿瘤大小、淋巴结转移及TNM分期密切相关(P<0.05),而与患者年龄、性别、分化、浸润深度及远处转移无显著相关性(P>0.05)。K-M生存分析结果表明,NPAS2高表达组患者5年生存率显著高于低表达组,差异具有统计学意义(P<0.01)。结论NPAS2在结直肠癌组织中低表达,且与肿瘤部分恶性生物学行为及患者5年生存率密切相关,提示检测NPAS2的表达对预测结直肠癌患者预后具有重要意义。展开更多
神经元PAS结构域蛋白2(neuronal PAS domain protein 2,NPAS2)是目前发现最大的核心生物节律基因,通过与BMAL1形成异源二聚体作为转录因子参与生物钟的调控,在细胞功能和肿瘤发生中发挥重要作用。近年来越来越多的证据显示,节律基因的...神经元PAS结构域蛋白2(neuronal PAS domain protein 2,NPAS2)是目前发现最大的核心生物节律基因,通过与BMAL1形成异源二聚体作为转录因子参与生物钟的调控,在细胞功能和肿瘤发生中发挥重要作用。近年来越来越多的证据显示,节律基因的紊乱与肿瘤的发生、发展密切相关,NPAS2基因突变和多态性也与肿瘤的发生有一定关系,其表达可影响多种肿瘤的发生和预后。NPAS2可以通过调控细胞周期、增殖和代谢参与肿瘤的发生和进程,并已在肝癌、乳腺癌和子宫内膜癌等肿瘤中得到证实,有望成为肿瘤新的治疗靶点和预后标志物。本文就NPAS2在肿瘤中作用的研究进展进行综述。展开更多
目的采用逍遥散干预慢性应激损伤模型大鼠,观察其海马区神经PAS域蛋白2(neuronal PASdomain protein 2,Npas2)基因的表达及其DNA特定区域甲基化的修饰情况。方法将90只雄性Wistar大鼠随机分为空白对照组、慢性应激模型组和逍遥散治疗组,...目的采用逍遥散干预慢性应激损伤模型大鼠,观察其海马区神经PAS域蛋白2(neuronal PASdomain protein 2,Npas2)基因的表达及其DNA特定区域甲基化的修饰情况。方法将90只雄性Wistar大鼠随机分为空白对照组、慢性应激模型组和逍遥散治疗组,共3组,每组30只。造模采用Cart多相慢性应激大鼠模型并加以改进,逍遥散治疗组在造模同时每天给予逍遥散2 m L,连续造模21 d。采用RT-PCR一步法及免疫组织化学染色法测定各组大鼠海马区Npas2基因及其蛋白表达情况,基因甲基化检测采用SequenomMass ARRAY法。结果慢性应激损伤大鼠海马Npas2m RNA及其相应蛋白表达有明显变化,与空白对照组和逍遥散治疗组比较差异均有统计学意义,但其m RNA及相应蛋白表达变化趋势不一致,其基因某些特定区域的甲基化程度有升高的趋势(个别位点有统计学差异)。逍遥散治疗能够明显逆转慢性应激引起的Npas2m RNA及其相应蛋白的表达变化,相应区域DNA甲基化程度表现出下调趋势(个别位点有统计学差异)。结论 Npas2基因参与了慢性应激损伤过程,其表达变化可能与其基因某些特定位点的甲基化修饰变化有关,逍遥散能够逆转这种表达改变,可能是通过调节Npas2基因特定位点的甲基化程度发挥作用。展开更多
目的探讨神经元PAS结构域蛋白2(neuronal PAS domain protein 2,NPAS2)在急性髓系白血病(acute myeloid leukemia,AML)患者和细胞系中的表达变化,及其对AML细胞生长的作用。方法收集陕西省西安市中心医院血液病研究所2013—2017年收治...目的探讨神经元PAS结构域蛋白2(neuronal PAS domain protein 2,NPAS2)在急性髓系白血病(acute myeloid leukemia,AML)患者和细胞系中的表达变化,及其对AML细胞生长的作用。方法收集陕西省西安市中心医院血液病研究所2013—2017年收治的初诊急性髓系白血病患者46例,实时定量PCR方法检测NPAS2在AML患者及正常对照组骨髓单个核细胞中的表达,Western blot方法检测AML细胞系及对照组中NPAS2的表达;统计学方法分析NPAS2表达高低对AML患者预后的影响;RNAi方法干扰AML细胞内NPAS2表达,利用CCK-8法检测NPAS2对细胞生长的作用。结果 NPAS2在AML患者及细胞系中的表达较对照组升高(P<0.05);在M1、M2、M3、M4、M5患者中NPAS2表达较对照组升高(P<0.05),在M6和M7患者中其表达较对照组差异无统计学意义(P>0.05);高表达NPAS2的AML患者其总体生存期较低表达患者短(P<0.05);AML细胞中干涉NPAS2后,与对照组比,干涉组细胞生长明显减慢(P<0.05)。结论 NPAS2在AML患者中表达上调并与AML患者预后负相关,同时NPAS2促进AML细胞生长。展开更多
文摘BACKGROUND The prognostic assessment of patients after surgical resection of gastric cancer(GC)patients is critical.However,the role of the circadian clock gene NPAS2 expression in GC remains unknown.AIM To explore the relationship between NPAS2 and the survival prognosis of GC patients and clarify its role in evaluating GC prognosis.METHODS The tumor tissues and clinical data of 101 patients with GC were collected retrospectively.Immunohistochemical staining(IHC)was used to detect the expression of NPAS2 protein in GC and adjacent tissues.Univariate and multivariate Cox regression analysis was used to determine the independent prognostic factors of GC,and a nomogram prediction model was established.The receiver operating characteristic(ROC)curve,the ROC area under the curve,the calibration curve,and C-index were used to evaluate the predictive effectiveness of the model.Kaplan Meier analysis was used to compare the risk stratification of subgroups according to the median score in the nomogram model of each patient.RESULTS Microarray IHC analysis showed that the positive rate of NPAS2 protein expression in GC tissues was 65.35%,which was significantly higher than 30.69%in adjacent tissues.The high expression of NPAS2 was correlated with tumor-node-metastasis(TNM)stage(P<0.05),pN stage(P<0.05),metastasis(P<0.05),venous invasion(P<0.05),lymphatic invasion(P<0.05),and lymph node positive(P<0.05)of GC.Kaplan Meier survival analysis showed that the 3-year overall survival(OS)of patients with high NPAS2 expression was significantly shortened(P<0.0001).Univariate and multivariate COX regression analysis showed that TNM stage(P=0.009),metastasis(P=0.009),and NPAS2 expression(P=0.020)were independent prognostic factors of OS in GC patients for 3 years.The nomogram prediction model based on independent prognostic factors has a C-Index of 0.740(95%CI:0.713-0.767).Furthermore,subgroup analysis showed that the 3-year OS time of the high-risk group was significantly lower than that of the low-risk group(P<0.0001).CONCLUSION NPAS2 is highly expressed in GC tissues and is closely related to worse OS in patients.Therefore,the evaluation of NPAS2 expression may be a potential marker for GC prognosis evaluation.Notably,the nomogram model based on NPAS2 can improve the accuracy of GC prognosis prediction and assist clinicians in postoperative patient management and decision-making.
文摘目的检测生物节律基因NPAS2在结直肠癌组织及相应癌旁组织中的表达情况;明确NPAS2的表达与患者临床病理学参数之间的相关性,分析NPAS2表达与结直肠癌患者5年生存率之间的相关性,明确其在判断结直肠癌患者预后中的作用。方法采用RT-q PCR检测NPAS2 m RNA在40例结直肠癌及癌旁新鲜组织中的表达;采用免疫组织化学SABC法检测NPAS2蛋白在120例肿瘤及癌旁石蜡标本中的表达;利用其中78例随访患者资料,K-M生存法分析NPAS2蛋白表达水平与患者生存率之间的相关性。结果 RT-q PCR结果提示,结直肠癌中NPAS2 m RNA表达显著低于相对应的癌旁组织(P<0.01);免疫组织化学结果提示,NPAS2蛋白表达在结直肠癌组织中的阳性率为19.2%,显著低于癌旁中的62.5%(P<0.05)。NPAS2的低表达与结直肠癌的肿瘤大小、淋巴结转移及TNM分期密切相关(P<0.05),而与患者年龄、性别、分化、浸润深度及远处转移无显著相关性(P>0.05)。K-M生存分析结果表明,NPAS2高表达组患者5年生存率显著高于低表达组,差异具有统计学意义(P<0.01)。结论NPAS2在结直肠癌组织中低表达,且与肿瘤部分恶性生物学行为及患者5年生存率密切相关,提示检测NPAS2的表达对预测结直肠癌患者预后具有重要意义。
文摘神经元PAS结构域蛋白2(neuronal PAS domain protein 2,NPAS2)是目前发现最大的核心生物节律基因,通过与BMAL1形成异源二聚体作为转录因子参与生物钟的调控,在细胞功能和肿瘤发生中发挥重要作用。近年来越来越多的证据显示,节律基因的紊乱与肿瘤的发生、发展密切相关,NPAS2基因突变和多态性也与肿瘤的发生有一定关系,其表达可影响多种肿瘤的发生和预后。NPAS2可以通过调控细胞周期、增殖和代谢参与肿瘤的发生和进程,并已在肝癌、乳腺癌和子宫内膜癌等肿瘤中得到证实,有望成为肿瘤新的治疗靶点和预后标志物。本文就NPAS2在肿瘤中作用的研究进展进行综述。
文摘目的探讨神经元PAS结构域蛋白2(neuronal PAS domain protein 2,NPAS2)在急性髓系白血病(acute myeloid leukemia,AML)患者和细胞系中的表达变化,及其对AML细胞生长的作用。方法收集陕西省西安市中心医院血液病研究所2013—2017年收治的初诊急性髓系白血病患者46例,实时定量PCR方法检测NPAS2在AML患者及正常对照组骨髓单个核细胞中的表达,Western blot方法检测AML细胞系及对照组中NPAS2的表达;统计学方法分析NPAS2表达高低对AML患者预后的影响;RNAi方法干扰AML细胞内NPAS2表达,利用CCK-8法检测NPAS2对细胞生长的作用。结果 NPAS2在AML患者及细胞系中的表达较对照组升高(P<0.05);在M1、M2、M3、M4、M5患者中NPAS2表达较对照组升高(P<0.05),在M6和M7患者中其表达较对照组差异无统计学意义(P>0.05);高表达NPAS2的AML患者其总体生存期较低表达患者短(P<0.05);AML细胞中干涉NPAS2后,与对照组比,干涉组细胞生长明显减慢(P<0.05)。结论 NPAS2在AML患者中表达上调并与AML患者预后负相关,同时NPAS2促进AML细胞生长。
