目的检测动力蛋白激活蛋白2(dynactin 2,DCTN2)和肿瘤高表达细胞周期相关蛋白(cell-cycle-related and expression-elevated protein in tumor,CREPT)在胃癌组织和癌旁组织中的表达差异性,探讨DCTN2和CREPT表达与胃癌患者的临床病理特...目的检测动力蛋白激活蛋白2(dynactin 2,DCTN2)和肿瘤高表达细胞周期相关蛋白(cell-cycle-related and expression-elevated protein in tumor,CREPT)在胃癌组织和癌旁组织中的表达差异性,探讨DCTN2和CREPT表达与胃癌患者的临床病理特征及预后的关系。方法纳入2014年3月~2015年9月于徐州医科大学附属医院行胃癌切除术并经组织病理学证实为胃癌的患者90例,采用免疫组织化学法检测DCTN2和CREPT在胃癌组织及癌旁组织中的表达水平,采用Spearman法分析胃癌组织中DCTN2与CREPT的表达相关性;分析DCTN2与CREPT表达水平与胃癌患者临床病理特征的关系;采用Kaplan-Meier法及Log-rank法分析DCTN2和CREPT的表达水平对胃癌患者生存期的影响;通过单因素及多因素COX回归分析影响胃癌患者预后的独立危险因素。结果胃癌组织中DCTN2和CREPT的表达水平显著高于癌旁组织,且两者的表达呈正相关(P<0.05);DCTN2和CREPT的表达水平与胃癌分化程度、TNM分期、肿瘤浸润深度、淋巴结转移情况显著相关(P<0.05),与患者的性别、年龄、远处转移情况无明显相关性(P>0.05);预后分析结果显示,DCTN2高表达组胃癌患者的术后1、3、5年累积生存率及总生存率均显著低于DCTN2低表达组,CREPT高表达组胃癌患者的术后5年累积生存率和总生存率均显著低于CREPT低表达组(P<0.05)。单因素及多因素COX回归分析结果显示,DCTN2和CREPT均是影响胃癌患者预后的独立危险因素。结论DCTN2和CREPT在胃癌组织中均显著高表达,其高表达与胃癌患者的不良预后密切相关,有望成为胃癌诊断的潜在标志物和治疗新靶点,并有助于判断胃癌患者的预后。展开更多
Background:Dynactin(DCTN)can activate cytoplasmic dynein and drive intracellular organelle transport containing six family members(DCTN1 to DCTN6).The DCTN family has been studied as cancer-related genes or biomarkers...Background:Dynactin(DCTN)can activate cytoplasmic dynein and drive intracellular organelle transport containing six family members(DCTN1 to DCTN6).The DCTN family has been studied as cancer-related genes or biomarkers in various cancers.Nevertheless,in hepatocellular carcinoma(HCC),the functions and prognostic roles of the DCTN family have been unexplored.Methods:We evaluated the diagnostic and survival effects of DCTN subunits in HCC through bioinformatics analysis and validated the results of bioinformatics by our data to address this problem.Results:The results of bioinformatics analysis found that DCTN2 was a significant prognostic factor in HCC,and high-level DCTN2 can predict poor patient survival in HCC.Cox regression analysis also suggested that DCTN2(hazard ratio=1.748,95%confidence interval 1.190-2.568,P=0.004)is an independent prognostic factor for patient survival.Western blot and quantitative reverse transcriptionpolymerase chain reaction assays confirmed that the protein and mRNA expression levels of DCTN2 were upregulated in HCC cell lines.The proliferation,invasion,and migration were decreased and cell apoptosis was enhanced after DCTN2 was knocked down in Huh7 and Hep3B cells.DCTN2 promoted the cell cycle progression through regulating the expression of cell cycle regulatory proteins cyclindependent kinase 4,Cyclin D1,and p21.Conclusions:We propose that DCTN2 can serve as a prognostic marker for HCC.DCTN2 acts as an oncogene and promotes the cell cycle progression through the G1/S phase-related signaling pathway.展开更多
文摘目的检测动力蛋白激活蛋白2(dynactin 2,DCTN2)和肿瘤高表达细胞周期相关蛋白(cell-cycle-related and expression-elevated protein in tumor,CREPT)在胃癌组织和癌旁组织中的表达差异性,探讨DCTN2和CREPT表达与胃癌患者的临床病理特征及预后的关系。方法纳入2014年3月~2015年9月于徐州医科大学附属医院行胃癌切除术并经组织病理学证实为胃癌的患者90例,采用免疫组织化学法检测DCTN2和CREPT在胃癌组织及癌旁组织中的表达水平,采用Spearman法分析胃癌组织中DCTN2与CREPT的表达相关性;分析DCTN2与CREPT表达水平与胃癌患者临床病理特征的关系;采用Kaplan-Meier法及Log-rank法分析DCTN2和CREPT的表达水平对胃癌患者生存期的影响;通过单因素及多因素COX回归分析影响胃癌患者预后的独立危险因素。结果胃癌组织中DCTN2和CREPT的表达水平显著高于癌旁组织,且两者的表达呈正相关(P<0.05);DCTN2和CREPT的表达水平与胃癌分化程度、TNM分期、肿瘤浸润深度、淋巴结转移情况显著相关(P<0.05),与患者的性别、年龄、远处转移情况无明显相关性(P>0.05);预后分析结果显示,DCTN2高表达组胃癌患者的术后1、3、5年累积生存率及总生存率均显著低于DCTN2低表达组,CREPT高表达组胃癌患者的术后5年累积生存率和总生存率均显著低于CREPT低表达组(P<0.05)。单因素及多因素COX回归分析结果显示,DCTN2和CREPT均是影响胃癌患者预后的独立危险因素。结论DCTN2和CREPT在胃癌组织中均显著高表达,其高表达与胃癌患者的不良预后密切相关,有望成为胃癌诊断的潜在标志物和治疗新靶点,并有助于判断胃癌患者的预后。
基金This work was funded by the National Natural Science Foundation of China(No.81702375)the Natural Science Foundation of Guangdong Province of China(No.2021A15150124)+1 种基金the Sun Yatsen university young teacher training program(No.19ykpy32)the Scientific Research Project of Dongguan Binhaiwan Central Hospital(No.2021001).
文摘Background:Dynactin(DCTN)can activate cytoplasmic dynein and drive intracellular organelle transport containing six family members(DCTN1 to DCTN6).The DCTN family has been studied as cancer-related genes or biomarkers in various cancers.Nevertheless,in hepatocellular carcinoma(HCC),the functions and prognostic roles of the DCTN family have been unexplored.Methods:We evaluated the diagnostic and survival effects of DCTN subunits in HCC through bioinformatics analysis and validated the results of bioinformatics by our data to address this problem.Results:The results of bioinformatics analysis found that DCTN2 was a significant prognostic factor in HCC,and high-level DCTN2 can predict poor patient survival in HCC.Cox regression analysis also suggested that DCTN2(hazard ratio=1.748,95%confidence interval 1.190-2.568,P=0.004)is an independent prognostic factor for patient survival.Western blot and quantitative reverse transcriptionpolymerase chain reaction assays confirmed that the protein and mRNA expression levels of DCTN2 were upregulated in HCC cell lines.The proliferation,invasion,and migration were decreased and cell apoptosis was enhanced after DCTN2 was knocked down in Huh7 and Hep3B cells.DCTN2 promoted the cell cycle progression through regulating the expression of cell cycle regulatory proteins cyclindependent kinase 4,Cyclin D1,and p21.Conclusions:We propose that DCTN2 can serve as a prognostic marker for HCC.DCTN2 acts as an oncogene and promotes the cell cycle progression through the G1/S phase-related signaling pathway.
