血清吲哚胺2,3-双加氧酶与早期非小细胞肺癌立体定向放射治疗预后的相关性

The association between indoleamine 2,3-dioxygenase activity and clinical prognosis in patients with early stage non-small cell lung cancer after stereotactic radiotherapy

目的探索早期非小细胞肺癌(NSCLC)体部立体定向放射治疗(SBRT)前后血清中吲哚胺2,3-双加氧酶(IDO)活性的变化以及与患者生存的相关性。方法本研究为回顾性研究,通过血清犬尿氨酸(Kyn)及Kyn:色氨酸(Trp)比值评估早期NSCLC患者SBRT治疗前后IDO的活性。纳入2014年12月至2017年7月间在中国科学院大学附属肿瘤医院接受SBRT治疗的30例早期NSCLC患者,利用高效液相色谱法测定其SBRT治疗前后血清Kyn、Trp浓度。根据中位数为截断值,将放疗后与放疗前Kyn浓度比值分为Kyn高水平组和Kyn低水平组。同理,将放疗后Kyn:Trp比值分为放疗后Kyn:Trp高水平组和放疗后Kyn:Trp低水平组。分析患者总生存率(OS)、无进展生存率(PFS)和IDO活性的相关性以及影响患者预后的相关因素。结果放疗后Kyn与放疗前Kyn比值较低组可获得较长的PFS(中位数:未达到vs.26.8个月,HR=0.31,95%CI=0.11~0.90,P<0.05)。放疗后Kyn:Trp比值较低组可获得较长的OS(中位数:未达到vs.36.5个月,HR=0.27,95%CI=0.08~0.95,P<0.05)。多因素分析中,吸烟<30包/年、高生物等效剂量(BED)、放疗后Kyn与放疗前Kyn比值较低与较长的PFS相关。放疗后Kyn:Trp较低、高BED与较长的OS相关。结论SBRT可以改变IDO介导的抗肿瘤免疫活性。IDO是一种潜在的重要生物标志物,可用于监测早期NSCLC患者SRRT治疗后的免疫状态,对预测患者生存有一定价值。

Objective To explore the changes in activity of indoleamine 2,3-dioxygenase(IDO)before and after stereotactic body radiation therapy(SBRT)in early stage non-small cell lung cancer(NSCLC)and its relationship with survival.Methods The retrospective study was to assess IDO activity by serum kynurenine(Kyn)and Kyn to tryptophan(Trp)ratio before and after SBRT of early stage NSCLC.Thirty early stage NSCLC patients who received SBRT in the Cancer Hospital of the University of Chinese Academy of Sciences were enrolled,from December 2014 to July 2017.High-performance liquid chromatography and mass spectrometry were used to detect serum Kyn and Trp before and after SBRT.The ratios of Kyn after SBRT to Kyn before SBRT were divided into high and low group according to the median value.Similarly,the ratios of Kyn to Trp after SBRT were divided into high and low group.The correlation between overall survival(OS),progression-free survival(PFS)and IDO activity was evaluated.The factors influencing prognosis were analyzed.Results In all patients,lower ratio of Kyn after SBRT to Kyn before SBRT significantly was correlated with better PFS(median PFS:not reached vs.26.8 months,HR=0.31,95%CI=0.11-0.90,P<0.05).The lower Kyn:Trp ratio after SBRT had longer OS(median OS:not reached vs.36.5 months,HR=0.27,95%CI=0.079-0.95,P<0.05).In multivariate analysis,smoking<30 packs/year,higher BED,and lower ratio of Kyn after SBRT to Kyn before SBRT were associated with longer PFS.Lower Kyn:Trp ratio after SBRT and higher BED were associated with longer OS.Conclusions SBRT could alter IDO-mediated antitumor immune activity.IDO is a potentially valuable biomarker for monitoring immune status and predicting survival in early NSCLC patients after SBRT.