CUL4B、TRPM2在胰腺癌组织中的表达和临床意义

Expression and clinical significance of CUL4B and TRPM2 in pancreatic cancer

目的探讨胰腺癌组织中E3泛素连接酶Cullin4B(CUL4B)、人瞬时受体电位M2(TRPM2)的表达及临床意义。方法收集2019年3月—2020年3月在西安交通大学医学院附属3201医院接受手术治疗胰腺癌患者86例的癌组织和癌旁组织。采用免疫组织化学检测组织中CUL4B、TRPM2蛋白表达。采用实时荧光定量PCR检测组织中CUL4B、TRPM2 mRNA水平。Spearman秩相关分析CUL4B与TRPM2蛋白表达的关系。Kaplan-Meier曲线分析CUL4B、TRPM2蛋白表达对患者预后的影响。Cox比例风险模型分析胰腺癌预后影响因素。结果胰腺癌组织中CUL4B、TRPM2蛋白阳性率及mRNA基因的相对表达量高于癌旁组织(χ^(2)/t=70.245、60.224、15.741、10.976,P均<0.001)。胰腺癌组织中CUL4B与TRPM2蛋白表达呈显著正相关(r=0.720,P<0.001)。TNM分期ⅡB~Ⅲ期、淋巴结转移胰腺癌中CUL4B、TRPM2蛋白阳性率高于Ⅰ~ⅡA期、无淋巴结转移癌组织(χ^(2)=16.511、14.834,15.576、15.007,P均<0.001)。CUL4B阳性组和阴性组3年总生存率分别为9.68%(6/62)、41.67%(10/24),TRPM2阳性组和阴性组3年总生存率分别为8.33%(5/60)、42.31%(11/26),CUL4B阳性组、TRPM2阳性组患者3年累积生存率低于CUL4B阴性组、TRPM2阴性组患者(Log-Rankχ^(2)/P=9.933/0.002、11.102/0.001)。TNM分期ⅡB~Ⅲ期、淋巴结转移、CUL4B阳性、TRPM2阳性是影响胰腺癌不良预后的独立危险因素[HR(95%CI)=1.781(1.199~2.646),1.962(1.172~3.285),2.482(1.445~4.263),1.733(1.223~2.457)]。结论胰腺癌组织中CUL4B、TRPM2表达升高,两者表达与胰腺癌不良临床病理特征有关,是胰腺癌预后相关肿瘤标志物。

Objective To investigate the expression and clinical significance of Cullin4B E3 ubiquitin ligase(CUL4B)and human transient receptor potential M2(TRPM2)in pancreatic cancer.Methods Eighty-six patients with pancreatic cancer who were diagnosed and treated in author’s hospital from March 2019 to March 2020 were selected.Immunohistochemistry was used to detect the expression of CUL4B and TRPM2 proteins in tissues.Real time fluorescence quantitative PCR was used to detect the expression of CUL4B and TRPM2 mRNA in tissues.Spearman rank correlation analysis was used to analyze the relationship between CUL4B and TRPM2 protein expression.Kaplan-Meier curve analysis was used to analyze the impact of CUL4B and TRPM2 expression on patient prognosis.Cox proportional hazards model was used to analyze the prognostic factors of pancreatic cancer.Results The positive rate of CUL4B and TRPM2 protein and the relative expression of mRNA in pancreatic cancer tissues were higher than those in adjacent tissues,and the difference was statistically significant(χ^(2)/t=70.245,60.224,15.741,10.976,P<0.001).The expression of CUL4B was positively correlated with TRPM2 in pancreatic cancer(r=0.720,P<0.001).The positive rates of CUL4B and TRPM2 protein in TNM stageⅡB-Ⅲ,lymph node metastasis pancreatic cancer were higher than those in stageⅠ-ⅡA,and no lymph node metastasis(χ^(2)=16.511,14.834,15.576,15.007,P<0.001).The 3-year overall survival rates of the CUL4B positive and negative groups were 9.68%(6/62)and 41.67%(10/24),respectively.The 3-year overall survival rates of the TRPM2 positive and negative groups were 8.33%(5/60)and 42.31%(11/26),respectively.The 3-year cumulative survival rate of patients in the CUL4B positive group and TRPM2 positive group was lower than that in the CUL4B negative group and TRPM2 negative group,and the difference was statistically significant(Log-Rankχ^(2)=9.933,11.102,P=0.002,0.001).TNM stage,lymph node metastasis,CUL4B,TRPM2 were independent factors affecting the prognosis of pancreatic cancer[HR(95%CI)=1.781(1.199-2.646),1.962(1.172-3.285),2.482(1.445-4.263),1.733(1.223-2.457)].Conclusion The expression of CUL4B and TRPM2 in pancreatic cancer are elevated,which are related to the poor clinicopathological characteristics of pancreatic cancer and are prognostic tumor markers of pancreatic cancer.