肝细胞癌中精氨酸酶1和诱导型一氧化氮合成酶表达的临床意义及其相关性研究

Study on the clinical significance and correlation of arginase-1 and inducible nitric oxide synthase expression in hepatocellular carcinoma

目的探讨精氨酸酶1(Arg-1)和诱导型一氧化氮合成酶(iNOS)在肝细胞癌(HCC)中表达的相关性及临床意义。方法采用免疫组织化学法检测146例肝细胞癌及对应癌旁组织中Arg-1和iNOS的表达,采用χ2检验、Spearman等级相关分析、Kaplan-Meier生存分析及Cox多因素分析等统计学方法,分析两者表达的临床病理特征及其相关性和预后的关系。结果Arg-1和iNOS的阳性率分别为18.7%(23/123)和37.0%(54/146),明显低于癌旁组织100%(146/146)和93.8%(137/146),差异有统计学意义(χ^2=212.521,P<0.01,χ^2=104.276,P<0.01);两者表达存在一定的正相关性(r=0.331,P<0.01)。Arg-1低表达与术前血清甲胎蛋白(AFP)水平、肿瘤大小、分化程度、组织学类型及Edmondson分级相关,iNOS低表达与分化程度、Edmondson分级相关性(P<0.05)。Kaplan-Meier生存分析显示,患者无复发生存期(RFS)Arg-1(+)组>Arg-1(-)组以及Arg-1(+)iNOS(+)组>Arg-1(+)iNOS(-)组>Arg-1(-)iNOS(+)组>Arg-1(-)iNOS(-)组(P<0.05);COX多因素分析显示年龄、肿瘤大小、Edmondson分级、脉管癌栓与RFS显著相关(P值均<0.05)。结论在HCC中Arg-1与iNOS表达存在正相关性,两者均可反映HCC的恶性程度,两者降低/缺失表达可能协同参与了HCC的发生与发展,联合检测Arg-1与iNOS对HCC的分化程度及预后判断可能具有一定的意义。

Objective To investigate the clinical significance and correlation of arginase 1(Arg-1)and inducible nitric oxide synthase(iNOS)expression in hepatocellular carcinoma(HCC).Methods The expression of Arg-1and iNOS in 146 cases of hepatocellular carcinoma tissues and corresponding adjacent tissues was detected by immunohistochemistry.The clinicopathological characteristics and the correlation between the expressions and prognosis were determined by chi square test,Spearman’s rank correlation,Kaplan-Meier survival analysis and Cox regression analysis.Results The positive rates of Arg-1 and iNOS were 18.7%(23/123)and 37.0%(54/146),respectively,which was significantly lower than the adjacent tissues[100%(146/146)and 93.8%(137/146)]and the difference was statistically significant(χ^2=212.521,P<0.01,χ^2=104.276,P<0.01).There was a positive correlation between the both expression(r=0.331,P<0.01).Arg-1 low expression was correlated with preoperative serum alpha-fetoprotein(AFP)level,tumor size,differentiation degree,histological types and Edmondson’s grade.iNOS low expression was correlated with the differentiation degree and Edmondson’s grade(P<0.05).Kaplan Meier survival analysis showed that in patients with recurrence-free survival(RFs),Arg-1(+)group>Arg-1(-)group and Arg-1(+)iNOS(+)group>Arg-1(+)iNOS(-)group>Arg-1(-)iNOS(-)group(P<0.05).Cox multivariate analysis showed that age,tumor size,Edmondson’s grade,vascular tumor emboli were significantly correlated with RFs(P<0.05).Conclusion There is a positive correlation between Arg-1 and iNOS expressions in HCC,and both may reflect the HCC malignant degree.The reduced/absent expression of both may participate in the occurrence and development of HCC.The combined detection of Arg-1 and iNOS on HCC may have certain significance for the judgment of differentiation degree and prognosis.