肝细胞肝癌组织中程序性死亡配体-1表达与临床病理因素和预后的相关性

Correlation between the expression of programmed death ligand-1 and clinicopathological factors and prognosis in hepatocellular carcinoma tissues

目的探讨肝细胞肝癌(HCC)组织中程序性死亡配体-1(PD-L1)的表达与临床病理参数和预后的相关性。方法连续纳入2008年1月至2016年12月在南通大学附属南通第三医院接受手术的344例HCC患者,应用组织芯片结合免疫组织化学方法检测病理石蜡样本HCC组织中PD-L1的表达,分析PD-L1在肿瘤细胞和肿瘤浸润免疫细胞中的表达与HCC临床病理参数和预后的相关性,探讨影响患者预后的相关因素。统计学方法采用卡方检验、log-rank检验、单因素和多因素Cox比例风险回归模型分析。结果PD-L1阳性信号定位于HCC肿瘤细胞和肿瘤浸润免疫细胞的细胞膜和(或)细胞质上。肿瘤细胞中PD-L1阳性表达率为21.8%(75/344)。肿瘤细胞中PD-L1的阳性表达与肿瘤组织学分级、微血管侵犯有关,组织学分级Ⅰ、Ⅱ、Ⅲ级患者的PD-L1表达阳性率分别为7.7%(2/26)、16.5%(19/115)、26.6%(54/203),有微血管侵犯和无微血管侵犯的患者PD-L1表达阳性率分别为29.3%(34/116)、18.0%(41/228),差异均有统计学意义(χ^2=7.659、5.787,P=0.022、0.016)。肿瘤浸润免疫细胞PD-L1阳性表达率为47.1%(162/344)。肿瘤浸润免疫细胞中PD-L1的表达与微血管侵犯有关,有微血管侵犯和无微血管侵犯的患者PD-L1阳性表达率分别为56.9%(66/116)、42.1%(96/228),差异有统计学意义(χ^2=6.751,P=0.009)。HCC肿瘤细胞中PD-L1阴性表达患者的中位生存时间为61个月(30个月,92个月),PD-L1阳性患者为16个月(6个月,44个月),差异有统计学意义(χ^2=55.722,P<0.01)。多因素Cox比例风险回归模型分析显示,PD-L1在HCC肿瘤细胞中的表达是影响总生存时间的独立危险因素[风险比(HR)=3.090,P<0.01]。结论PD-L1在HCC组织肿瘤细胞中的表达可能与肿瘤恶性程度、侵袭性相关,并且可能是潜在的预后危险因素。

Objective To investigate the correlation between the expression of programmed death ligand-1(PD-L1)and clinicopathological parameters and prognosis in hepatocellular carcinoma(HCC)tissues.Methods From January 2008 to December 2016,344 HCC patients underwent surgery in Nantong Third Hospital Affiliated to Nantong University were enrolled.The expression of PD-L1 in paraffin HCC tissues was detected by tissue microarray and immunohistochemistry.The correlation between the expression of PD-L1 in tumor cells,tumor-infiltrating immune cells and the clinicopathological parameters and prognosis of HCC patients were analyzed.And the related factors affecting the prognosis of patients were explored.Chi-square test,log-rank test and univariate and multivariate Cox regression analysis were used for statistical analysis.Results Positive PD-L1 located in the membrane and/or cytoplasm of HCC tumor cells and tumor-infiltrating immune cells.The positive rate of PD-L1 expression in tumor cells was 21.8%(75/344).The expression of PD-L1 in tumor cells was related to histological grade and microvascular invasion,the positive rates of PD-L1 expression of patients with histological gradeⅠ,ⅡandⅢwere 7.7%(2/26),16.5%(19/115)and 26.6%(54/203),respectively,the positive rates of PD-L1 expression of patients with or without microvascular invasion were 29.3%(34/116)and 18.0%(41/228),respectively,and the differences were statistically significant(χ^2=7.659 and 5.787,P=0.022 and 0.016).The positive expression rate of PD-L1 in tumor-infiltrating immune cells was 47.1%(162/344).The expression of PD-L1 in tumor-infiltrating immune cells was related with microvascular invasion,the positive rates of PD-L1 expression in patients with or without microvascular invasion were 56.9%(66/116)and 42.1%(96/228),respectively,and the differences were statistically significant(χ^2=6.751,P=0.009).The median survival time of patients with negative expression of PD-L1 in HCC tumor cells was 61 months(30 months,92 months),while that of patients with positive PD-L1 expression was 16 months(6 months,44 months),and the difference was statistically significant(χ^2=55.722,P<0.01).The expression of PD-L1 in HCC tumor cells was an independent risk factor affecting overall survival time(hazard ratio=3.090,P<0.01).Conclusions The expression of PD-L1 in HCC tumor cells may be related to the malignancy and invasion of HCC,and may be a potential risk factor for prognosis.