血清过氧化物酶3在原发性肝癌中的诊断价值及其对预后的影响研究

背景　原发性肝癌（PHC）是一种常见的消化系统恶性肿瘤，常因诊断延误而导致预后不佳，术后5年生存率为20%~40%。过氧化物酶3（PRDX3）是线粒体中的一种重要的抗氧化物酶，在多种恶性肿瘤中高表达，与肿瘤的发生、发展密切相关，但目前关于PRDX3对PHC的临床诊断及预后评估价值的研究较少。目的　探讨血清PRDX3在PHC中的诊断价值及其对PHC预后的影响。方法　选取2013年6月-2015年6月郑州人民医院收治的PHC患者86例纳入PHC组，选取同期在本院检查并确诊为肝硬化（LC）患者78例纳入LC组，再选取同期进行体检的健康者66例纳入对照组。收集受试者的一般临床资料，检测丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、甲胎蛋白（AFP）和血清PRDX3水平；收集PHC患者的Child-Pugh分级、TNM分期、最大肿瘤直径、肝内肿瘤数量、血管浸润比例；收集PHC患者的术后短期恢复情况，包括是否肝区疼痛、发热、发生术后并发症、复发/转移以及术后住院时间；统计PHC患者的术后生存期，随访截至2018年6月。采用受试者工作特征（ROC）曲线分析PRDX3对PHC的诊断效能；采用Kaplan-Meier法绘制生存曲线，比较采用Log-rank检验；采用单因素和多因素Cox比例风险回归分析探讨PHC患者预后的影响因素。结果　PHC组患者ALT、AST、AFP、PRDX3均高于对照组和LC组，LC组患者ALT、AST、PRDX3均高于对照组（P<0.05）。ROC曲线分析结果显示，以对照组为参照，血清PRDX3诊断LC和PHC的ROC曲线下面积（AUC）分别为0.690、0.886，灵敏度分别为52.56%、75.58%，特异度分别为84.85%、100.00%；以LC组为参照，血清PRDX3诊断PHC的AUC为0.780，灵敏度为67.44%，特异度为87.18%。以PRDX3为检验变量，以随访终止时PHC患者的生存状态为分类变量绘制ROC曲线，结果显示，PRDX3预测PHC患者预后的AUC为0.649，最佳临界值为243 mg/L，Youden指数为0.254，灵敏度为63.83%，特异度为61.54%。根据该最佳临界值将PHC患者分为低PRDX3组（n=41）和高PRDX3组（n=45）。高PRDX3组患者TNM分期Ⅲ期+Ⅳ期所占比例、最大肿瘤直径、血管浸润比例大于低PRDX3组（P<0.05）。随访终止时，86例PHC患者术后生存期为9~60个月，中位生存期为33个月。Log-rank检验结果显示，不同TNM分期、最大肿瘤直径、血管浸润比例、PRDX3水平患者生存率比较，差异均有统计学意义（P<0.05）；单因素及多因素Cox比例风险回归分析结果显示，TNM分期、最大肿瘤直径、血管浸润比例和PRDX3水平是PHC患者术后生存期的独立影响因素（P<0.05）。结论　术前血清PRDX3水平可作为PHC的早期诊断指标，并且TNM分期、最大肿瘤直径、血管浸润比例和PRDX3水平是PHC患者术后生存期的独立影响因素。

Diagnostic and Prognostic Value of Serum Peroxiredoxin 3 in Primary Hepatic Carcinoma

Background　Primary hepatic carcinoma（PHC） is a common malignant tumor of the digestive system，which often has a poor prognosis due to delayed diagnosis.The 5-year survival rate is about 20%-40% after surgery.Peroxidase 3（PRDX3），an important antioxidant enzyme in mitochondria，which is highly expressed in various malignant tumors，and is closely related to the occurrence and development of tumors.However，there are few studies on the clinical diagnostic and prognostic value of PRDX3 in PHC.Objective　To investigate the diagnostic and prognostic value of serum PRDX3 in patients with PHC.Methods　From People's Hospital of Zhengzhou，86 patients with PHC（PHC group），78 patients diagnosed with liver cirrhosis（LC） after examination（LC group），and 66 health examinees（control group） were enrolled during June 2013 to June 2015.General clinical data，serum levels of ALT，AST，alpha-fetoprotein（AFP），and PRDX3 of all participants，and Child-Pugh score，TNM staging，diameter of the maximum tumor，number of intrahepatic tumors，and percentage of vascular invasion，short-term postoperative recovery status（prevalence of liver pain，fever，postoperative complications，recurrence/metastasis，and postoperative hospital stay） as well as postoperative survival period of the PHC group were collected.The follow-up ended in June 2018.The receiver operating characteristic（ROC） curve was used to analyze the diagnostic performance of serum PRDX3 for PHC.Kaplan-Meier method was used to draw the survival curve and Log-rank test was used for comparison.Univariate and multivariate Cox proportional hazards regression models were used to analyze the survival prognostic factors of PHC patients.Results　The mean levels of ALT，AST，AFP and PRDX3 in the PHC group were higher than those of LC group and control group（P<0.05）.The mean levels of ALT，AST，and PRDX3 in the liver cirrhosis group were higher than those of the control group（P<0.05）.The results of the ROC curve analysis showed that the AUC of serum PRDX3 was 0.690 in diagnosing LC，with 52.56% sensitivity and 84.85% specificity，and was 0.886 in diagnosing PHC，with 75.58% sensitivity and 87.18% specificity，with the control group as the reference.And the AUC of serum PRDX3 in diagnosing PHC was 0.780，the sensitivity was 67.44%，and the specificity was 87.18%，with LC group as the reference.The analysis of ROC curve drawn with PRDX3 as the test variable and the survival state of PHC patients at the end of follow-up as the categorical variable demonstrated that the AUC of PRDX3 in predicting the prognosis of PHC patients was 0.649，the optimal cut-off value was 243 mg/L，the Youden index was 0.254，the sensitivity was 63.83%，and the specificity was 61.54%.PHC patients with PRDX3 greater than 243 mg/L（n=41） had higher percentages of TNM stage Ⅲ and stage Ⅳ，greater mean diameter of the maximum tumor，and higher percentage of vascular invasion compared with those with PRDX3 less than 243 mg/L（n=45）（P<0.05）.At the end of follow-up，the postoperative survival of 86 PHC patients was 9-60 months，with a median survival of 33 months.The Log-rank test showed that the overall survival in PHC patients differed significantly by TNM stage，maximum tumor diameter，prevalence of vascular invasion，and PRDX3 level（P<0.05）.Cox proportional hazards regression analyses showed that TNM stage，maximum tumor diameter，prevalence of vascular invasion，and PRDX3 were independent influencing factors for the postoperative survival of PHC patients（P<0.05）.Conclusion　Preoperative serum PRDX3 level can be used as an early diagnostic indicator of PHC.Moreover，it is also an independent factor associated with the postoperative survival in these patients，just like TNM stage，maximum tumor diameter and vascular invasion prevalence.