转移性肾癌中程序性死亡受体-配体1表达及预后研究

Expression of programmed cell death protein-ligand 1 in metastatic renal cell carcinoma and its relationship to prognosis

目的 探讨程序性死亡受体-配体1蛋白(PD-L1)表达与转移性肾癌(mRCC)患者临床及病理资料、生存之间的关系及其临床意义。方法 运用免疫组织化学方法对手术切除的269例mRCC标本进行PD-L1检测,对PD-L1表达与临床和病理参数进行相关分析,KM生存曲线分析及COX回归分析PD-L1表达与生存之间的关系。结果 PD-L1表达于肿瘤浸润免疫细胞(sPD-L1)及肿瘤细胞(tPD-L1),PD-L1表达与肿瘤组织类型(tPD-L1:χ2=15.944,P<0.05;sPD-L1:χ2=6.511,P<0.05)、Fuhrman分级有关(tPD-L1:χ2=13.862,P<0.05;sPD-L1:χ2=4.375,P<0.05);sPD-L1阳性表达患者预后较低表达患者差(中位总生存分别为20个月,51个月),药物亚组分析显示索拉非尼用药组PD-L1阳性表达与患者预后有关(tPD-L1:P<0.05;sPD-L1:P<0.05),舒尼替尼用药组中仅sPD-L1蛋白表达与患者总生存有关(P<0.05),多因素回归分析显示sPD-L1为mRCC患者预后的独立预测因子[风险比(HR)=2.196(1.515~3.182),P<0.05]。结论 sPD-L1高表达预示酪氨酸激酶抑制剂(TKIs)治疗mRCC患者不良预后。

Objective To determine whether programmed cell death protein-ligand 1 (PD-L1) impacts overall survival and associate with clinical and pathological data in patients with metastatic renal cell carcinoma (mRCC) treated with tyrosine kinase inhibitors (TKIs).Methods A total of 269 mRCC patients, from 2007 to 2017, treated with sunitinib or sorafenib in Zhongshan Hospital, Fudan University were included in the study. PD-L1 was assessed by immunohistochemistry on continuous paraffin embedded slides. Correlation analysis of PD-L1 expression and tumor clinical and pathological features. Kaplan-Meier method and COX regression model were applied in survival analyses.Results PD-L1 protein was expressed in stromal immune cells (sPD-L1) and tumor cells (tPD-L1). The expression of PD-L1 protein were associate with histologic type (tPD-L1: P<0.05;sPD-L1: P<0.05), and Fuhrman grade (tPD-L1: P<0.05;sPD-L1: P<0.05). Patients with sPD-L1 positive expression had poor prognosis (median overall survival was 20 months, 51 months). Subgroup analysis showed that PD-L1 positive expression in the sorafenib group was associated with prognosis (tPD-L1: P<0.05;sPD-L1: P<0.05), in the sunitinib group only sPD-L1 protein expression was associated with overall survival (P<0.05). Multivariate regression analysis showed that sPD-L1 was an independent and significant risk factor for overall survival in patients with mRCC (hazard ratio [hazard ratio (HR)=2.196 (1.515-3.182), P<0.05].Conclusion Our findings suggest that sPD-L1 positive expression is significantly associated with poor overall survival in mRCC patients treated with TKIs. It is expected that sPD-L1 can provide prediction for the prognosis of mRCC patients treated with TKIs.