奥拉帕利对铂敏感复发BRCA突变卵巢癌患者PD-1/PD-L1信号通路的影响

The effect of olaparib on the PD-1/PD-L1 signaling pathway in platinum-sensitive recurrent BRCA-mutant ovarian cancer patients

目的探讨奥拉帕利与含铂方案对铂敏感复发乳腺癌易感基因(BRCA)突变卵巢癌(OC)患者肿瘤血管生成相关因子及程序性死亡受体-1(PD-1)/程序性死亡-配体1(PD-L1)信号通路的影响。方法回顾性选取2018年5月至2020年5月该院95例铂敏感复发BRCA突变OC患者,依据治疗方案不同分为两组,对照组47例接受紫杉类+铂类治疗,观察组48例接受奥拉帕利片。对比两组疗效、安全性、肿瘤血管生成相关因子[血管生成素-2(Ang-2)、血管内皮生长因子(VEGF)、基质细胞衍生因子-1α(SDF-1α)]、外周血CD4^(+)T细胞PD-1、PD-L1水平。结果观察组DCR比对照组高,差异有统计学意义(P<0.05)。观察组恶心、疲劳与乏力、呕吐、贫血、腹泻、白细胞减少、中性粒细胞减少及食欲减退发生率与对照组比较,差异无统计学意义(P>0.05)。观察组治疗3、6个周期血清VEGF、Ang-2及SDF-1α水平低于对照组,差异有统计学意义(P<0.05)。观察组治疗3、6个周期外周血CD4^(+)T细胞PD-1、PD-L1水平低于对照组,差异有统计学意义(P<0.05)。结论奥拉帕利应用于铂敏感复发BRCA突变OC患者中,可调控PD-1/PD-L1信号通路,降低肿瘤血管生成相关因子水平,提升治疗效果。

Objective To investigate the effect of olaparib and platinum-based regimen on tumor angiogenesis-related factors and programmed death-1(PD-1)/programmed death-ligand 1(PD-L1)signaling pathway in platinum-sensitive relapsed breast cancer susceptibility gene(BRCA)mutation ovarian cancer(OC)patients.Methods A retrospective analysis was conducted on 95 platinum-sensitive recurrent BRCA mutation OC patients in a hospital from May 2018 to May 2020.The patients were divided into two groups based on their treatment regimen:the control group(47 cases)received paclitaxel plus platinum therapy,and the observation group(48 cases)received olaparib tablets.The efficacy,safety,tumor angiogenesis-related factors[angiogenin-2(Ang-2),vascular endothelial growth factor(VEGF),stromal cell-derived factor-1α(SDF-1α)],peripheral blood CD4^(+)T cells PD-1,PD-L1 levels were compared between the two groups.Results DCR in observation group was higher than that in control group,the difference was statistically significant(P<0.05).There was no significant difference in the incidence of nausea,fatigue and fatigue,vomiting,anemia,diarrhea,leukopenia,neutropenia and anorexia between the observation group and the control group(P>0.05).The serum levels of VEGF,Ang-2 and SDF-1αin the observation group were lower than those in the control group after 3 and 6 cycles of treatment,and the differ ences were statistically significant(P<0.05).The levels of peripheral blood CD4^(+)T cells PD-1 and PD-L1 in the observation group were lower than those in the control group at 3 and 6 cycles of treatment,and the difference was statistically significant(P<0.05).Conclusion Olaparib is used in platinum-sensitive relapsed BRCA mutation OC patients to regulate the PD-1/PD-L1 signaling pathway,reduce the levels of tumor angiogenesis-related factors,and improve therapeutic efficacy.