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不同的驱动基因突变对 NSCLC 中 PD-L1 表达的影响。

Various impacts of driver mutations on the PD-L1 expression of NSCLC.

机构信息

Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.

Division of Pulmonary Medicine, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan.

出版信息

PLoS One. 2022 Aug 18;17(8):e0273207. doi: 10.1371/journal.pone.0273207. eCollection 2022.

Abstract

We aimed to evaluate whether different driver mutations have varying impacts on the programmed cell death-ligand 1 (PD-L1) expression of non-small cell lung cancer (NSCLC), and whether the prognostic roles of PD-L1 amongst our patients were divergent. This was a single-institute study that included patients with NSCLC. Six driver mutations, PD-L1 status, and the outcomes of treatment were assessed. A total of 1,001 NSCLC patients were included for analysis. Overall, the PD-L1 positive (TPS ≥ 1%) and strong positive (TPS ≥ 50%) rates were 52.2% and 17.3%, respectively. As compared with wild type lung adenocarcinoma, EGFR-mutant and HER2-mutant patients had similarly low PD-L1 and strong PD-L1 positive rates. BRAF-mutant patients had numerically higher PD-L1 and strong PD-L1 positive rates. Patients with fusion mutation (ALK and ROS1) (aOR 2.32 [95% CI 1.10-4.88], P = 0.027 and 2.33 [95% CI 1.11-4.89], P = 0.026), KRAS mutation (aOR 2.58 [95% CI 1.16-5.75], P = 0.020 and 2.44 [95% CI 1.11-5.35], P = 0.026), and non-adenocarcinoma histology (aOR 2.73 [95% CI 1.72-4.34], P < 0.001 and 1.93 [95% CI 1.13-3.30], P = 0.016) all had significantly higher PD-L1 and strong PD-L1 positive rates. A trend towards longer survival was noted in ROS-1 rearranged and KRAS-mutant patients with strong PD-L1 expression who had received crizotinib and chemotherapy, respectively. In conclusion, individual driver mutations had various impacts on the PD-L1 expression of NSCLC patients. The prognostic role of PD-L1 may also be divergent amongst patients harboring different driver mutations.

摘要

我们旨在评估不同的驱动基因突变是否对非小细胞肺癌(NSCLC)的程序性死亡配体 1(PD-L1)表达产生不同的影响,以及我们的患者中 PD-L1 的预后作用是否存在差异。这是一项单中心研究,纳入了 NSCLC 患者。评估了 6 种驱动基因突变、PD-L1 状态和治疗结果。共纳入 1001 例 NSCLC 患者进行分析。总体而言,PD-L1 阳性(TPS≥1%)和强阳性(TPS≥50%)率分别为 52.2%和 17.3%。与野生型肺腺癌相比,EGFR 突变和 HER2 突变患者的 PD-L1 和强 PD-L1 阳性率同样较低。BRAF 突变患者的 PD-L1 和强 PD-L1 阳性率数值较高。融合突变(ALK 和 ROS1)患者(优势比 2.32[95%CI 1.10-4.88],P=0.027 和 2.33[95%CI 1.11-4.89],P=0.026)、KRAS 突变患者(优势比 2.58[95%CI 1.16-5.75],P=0.020 和 2.44[95%CI 1.11-5.35],P=0.026)和非腺癌组织学患者(优势比 2.73[95%CI 1.72-4.34],P<0.001 和 1.93[95%CI 1.13-3.30],P=0.016)的 PD-L1 和强 PD-L1 阳性率均显著较高。ROS1 重排和 KRAS 突变患者接受克唑替尼和化疗后,强 PD-L1 表达患者的生存时间有延长趋势。总之,不同的驱动基因突变对 NSCLC 患者的 PD-L1 表达有不同的影响。PD-L1 的预后作用在携带不同驱动基因突变的患者中也可能存在差异。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4124/9387808/f53607bdbdab/pone.0273207.g001.jpg

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