锌指蛋白18在胰腺导管腺癌组织中的表达及临床意义

Expression and clinical significance of zinc finger protein 18 in pancreatic ductal adenocarcinoma

目的检测锌指蛋白18(ZNF18)在胰腺导管腺癌(PDAC)组织的表达情况,分析其与PDAC临床病理特征和患者预后的关系。方法收集2017年3月至2019年12月间海军军医大学第一附属医院手术切除并经病理证实的131例PDAC患者的癌组织标本,采用免疫组织化学染色法检测癌组织ZNF18蛋白的表达,根据ZNF18表达水平将其分为ZNF18高表达组和低表达组,采用Kaplan-Meier法及Log-Rank检验分析比较ZNF18表达水平与PDAC患者总体生存期之间的关系。分析ZNF18蛋白表达水平与患者临床病理特征的相关性,应用单因素和多因素Cox回归模型分析影响PDAC患者预后的因素。结果131例PDAC组织中ZNF18高表达82例(62.60%),低表达49例(37.40%),ZNF18高表达组的总生存期显著长于低表达组[(21.53±0.69)个月比(12.17±1.57)个月],差异有统计学意义(P<0.001)。ZNF18低表达与肿瘤淋巴结转移有关(P<0.05),而与PDAC患者的性别、年龄、肿瘤位置、肿瘤大小、分化程度、TNM分期、神经侵犯、脉管癌栓无关。单因素分析结果显示,肿瘤分化程度、TNM分期、淋巴结转移及ZNF18表达水平均与PDAC患者的预后有关;多因素分析结果显示,肿瘤分化程度(HR=0.463,95%CI 0.279~0.769,P=0.003)、淋巴结转移(HR=2.062,95%CI 1.247~3.409,P=0.005)及ZNF18表达水平(HR=0.416,95%CI 0.255~0.676,P<0.001)为影响PDAC患者预后的独立危险因素。结论PDAC组织ZNF18低表达与肿瘤淋巴结转移及预后差密切相关,ZNF18可作为评估PDAC患者预后生存的潜在分子标志物。

Objective To investigate the expression of the zinc finger protein 18(ZNF18)in the pancreatic ductal adenocarcinoma(PDAC)tissue and analyze its relationship with the clinicopathological features and prognosis.Methods Cancer tissue specimens from 131 patients with PDAC who were surgically resected and pathologically confirmed at First Affiliated Hospital of Naval Medical University from March 2017 to December 2019 were collected.ZNF18 protein expression in cancer tissue was detected by immunohistochemical staining,and high and low ZNF18 expression groups were divided based on the expression level of ZNF18..Kaplan-Meier method and Log-Rank test were used to analyze the relationship between ZNF18 expression level and overall survival rate of PDAC patients.Furthermore,the correlation between ZNF18 protein expression level and clinicopathological features was analyzed,and the Cox regression hazards model was applied for the univariate and multivariate analysis of the factors affecting the prognosis of PDAC patients.Results 82 of 131(62.60%)PDAC tissues had high ZNF18 expression,and 49(37.40%)PDAC tissues had low ZNF18 expression;the survival time in the high ZNF18 expression group was significantly higher than that in the low ZNF18 expression group(21.53±0.69 months vs 12.17±1.57 months),and the difference was statistically significant(P<0.001).Low ZNF18 expression in PDAC was associated with lymph node metastasis(P<0.05),but was not correlated with gender,age,tumor location,tumor volume,differentiation degree,TNM stage,nerve invasion,and vascular cancer thrombus.The results of the univariate analysis showed that tumor differentiation degree,TNM stage,lymph node metastasis,and ZNF18 expression were all associated with the prognosis of PDAC patients.The results of the multivariate analysis showed that tumor differentiation degree(HR=0.463,95%CI 0.279-0.769,P=0.003),lymph node metastasis(HR=2.062,95%CI 1.247-3.409,P=0.005),and ZNF18 expression(HR=0.416,95%CI 0.255-0.676,P<0.001)were independent risk factors affecting the prognosis of patients with PDAC.Conclusions Low ZNF18 expression in PDAC tissues was closely associated with lymph node metastasis and poor prognosis.ZNF18 can be used as an important molecular marker to evaluate the prognostic survival of PDAC patients.