非小细胞肺癌组织Ki-67与PD-L1表达的相关性及其对患者预后的影响

Correlation between Ki-67 and PD-L1 expression in non-small cell lung cancer tissues and its effect on patients' prognosis

目的:探讨NSCLC患者癌组织中Ki-67与PD-L1表达的相关性及两者对患者预后的影响。方法:选取符合纳入标准的2012年1月至2018年8月在海军军医大学附属长海医院,手术确诊为NSCLC并进行免疫组化PD-L1和Ki-67检测的患者401例,收集其临床病理资料,定期生存随访,应用统计学方法分析Ki-67与PD-L1表达的相关性及两者对患者术后DFS和化疗后PFS的影响。结果:NSCLC组织中PD-L1和Ki-67表达阳性率分别为37.9%(152/401)和96.3%(386/401),单因素分析显示Ki-67为PDL1表达相关的影响因素(OR=0.33,95%CI=0.28～0.39,P<0.0001),曲线拟合分析显示Ki-67与PD-L1表达显著正相关,阈值效应分析、分段多因素Logistic和ROC曲线分析表明14%是Ki-67较适宜与PD-L1联用的阈值。Kaplan-Meier分析显示,术后DFS,Ki-67高表达组显著短于Ki-67低表达组[(21.88±11.25) vs (41.22±16.25)个月,P<0.0001],PD-L1阳性组显著短于PD-L1阴性组[(24.75±14.59) vs (38.27±16.75)个月,P<0.0001],Ki-67高表达/PD-L1阳性组与其余3组相比术后DFS最短[(20.57±11.33) vs(24.11±10.79) vs (36.00±16.79) vs (42.91±15.77)个月,P<0.0001];化疗PFS,Ki-67高表达组显著长于Ki-67低表达组[(7.70±3.01) vs(5.80±2.99)个月,P=0.016],PD-L1阳性组与阴性组相比差异无统计学意义[(7.04±3.21) vs (6.33±3.06)个月,P=0.22],Ki-67与PDL1联合测评,Ki-67高表达两组的PFS显著长于Ki-67低表达两组[(7.74±3.25) vs (7.43±2.38) vs(4.91±1.97) vs (6.02±3.19)个月,P=0.041]。结论:NSCLC组织中Ki-67与PD-L1表达呈正相关,Ki-67 14%是适宜与PD-L1联用的阈值,Ki-67和PD-L1均为患者预后不良的预测因子,两者联合对预后不良的预测有"叠加效应",同时Ki-67高表达患者对化疗的敏感性较好。

Objective:To investigate the relationship between Ki-67 and PD-L1 in patients with non-small cell lung cancer(NSCLC and their effects on prognosis.Methods:A total of 401 patients,who were pathologically diagnosed as NSCLC in Changhai Hospital from January 2012 to August 2018,were enrolled as study subjects;and the patients were immunohistochemically tested for PD-L1 and Ki-67.The clinical and pathological data were collected,and the follow-up was performed regularly.The correlation between Ki-67 and PD-L1 and their effects on postoperative DFS and post-chemotherapy PFS were statistically analyzed.Results:Positive rates of PD-L1 and Ki-67 in NSCLC tissues were 37.9%(152/401)and 96.3%(386/401),respectively.Univariate analysis showed that Ki-67 was an influencing factor for PD-L1 expression(OR=0.33,95%CI=0.28-0.39,P<0.0001);Curve Fitting analysis showed a positive correlation between Ki-67 and PD-L1;threshold effect analysis,segmentation multivariate logistic and ROC curve analysis showed 14%is a relatively suitable threshold for Ki-67 to be combined with PD-L1.Kaplan-Meier analysis showed that patients in Ki-67 high expression group had a significantly shorter post-operative DFS than those in Ki-67 low expression group([21.88±11.25]vs[41.22±16.25]m,P<0.0001),patients in PD-L1 positive group had a significantly shorter DFS than those in PD-L1 negative group([24.75±14.59]vs[38.27±16.75]m,P<0.0001)],and patients in Ki-67 high/PD-L1 positive group had the shortest DFS as compared to the other three groups([20.57±11.33]vs[24.11±10.79],[36.00±16.79],[42.91±15.77]m,P<0.0001).As for post-chemotherapy PFS,patients in Ki-67 high expression group was significantly longer than those in Ki-67 low expression group[(7.70±3.01)vs(5.80±2.99)m,P=0.016),but there was no significant difference between PD-L1 positive group and PD-L1 negative group[(7.04±3.21)vs(6.33±3.06)m,P=0.22);for combined evaluation with Ki-67 and PD-L1,the PFS of two Ki-67 high expression groups was significantly longer than the other two Ki-67 low expression groups[(7.74±3.25)vs(7.43±2.38)vs(4.91±1.97)vs(6.02±3.19)m,P=0.041).Conclusion:Ki-67 is positively correlated with PD-L1 in NSCLC patients,and Ki-67 14%is a suitable threshold for combined use with PD-L1.Both Ki-67 and PD-L1 are predictors of poor prognosis.The combination of the two has an"additive effect"on the prediction of poor prognosis,and patients with high Ki-67 expression are more sensitive to chemotherapy.