非小细胞肺癌中PD-L1表达与驱动基因状态的关联：一项荟萃分析。

Association between PD-L1 expression and driver gene status in non-small-cell lung cancer: a meta-analysis.

作者信息

Lan Bo, Ma Chengxi, Zhang Chengyan, Chai Shoujie, Wang Pingli, Ding Liren, Wang Kai

机构信息

Department of Respiratory Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Department of Oncology, Ningbo First Hospital, Ningbo, China.

出版信息

Oncotarget. 2018 Jan 5;9(7):7684-7699. doi: 10.18632/oncotarget.23969. eCollection 2018 Jan 26.

OBJECTIVE

To assess the association between PD-L1 expression and driver gene mutations in patients with non-small-cell lung cancer (NSCLC).

METHOD

We performed a meta-analysis of 26 studies (7541 patients) which were published from 2015 to 2017. Pooled odds ratios (ORs) with 95% confidence intervals (CI) were calculated to describe the correlation. Subgroup analysis was performed based on population characteristics, types of PD-L1 antibodies and quality of individual studies.

RESULTS

A lower frequency of PD-L1 positivity was observed in NSCLCs harboring EGFR mutation (OR: 0.64, 95% CI, 0.45-0.91, = 0.014). A negative correlation was also found at 1% (OR: 0.35, 95% CI, 0.22-0.55, = 0.000) and 50% (OR: 0.33, 95% CI, 0.14-0.81, = 0.015) cutoff for PD-L1 positive, elderly age group (OR: 0.56, 95% CI, 0.35-0.89, = 0.013), female dominant group (OR: 0.55, 95% CI, 0.29-0.94, = 0.030) and smoker dominant group (OR: 0.52, 95% CI, 0.29-0.96, = 0.035). No significant differences in PD-L1 expression were observed among patients with different ALK, BRAF, HER2, PIK3CA status and MET expression level. Higher level of PD-L1 was found in tumors with KRAS mutation (OR: 1.45, 95% CI, 1.18-1.80, = 0.001). PD-L1 expression level was not significantly different between triple (EGFR/ALK/KRAS) wild type NSCLCs and those with EGFR/ALK/KRAS mutation.

CONCLUSIONS

PD-L1 expression in EGFR mutated NSCLCs were lower than those in EGFR wild type NSCLCs, while tumors with KRAS mutation showed higher levels of PD-L1.

目的

评估非小细胞肺癌（NSCLC）患者中程序性死亡受体配体1（PD-L1）表达与驱动基因突变之间的关联。

方法

我们对2015年至2017年发表的26项研究（7541例患者）进行了荟萃分析。计算合并比值比（OR）及95%置信区间（CI）来描述相关性。基于人群特征、PD-L1抗体类型及个体研究质量进行亚组分析。

结果

在携带表皮生长因子受体（EGFR）突变的非小细胞肺癌中，观察到PD-L1阳性频率较低（OR：0.64，95%CI：0.45 - 0.91，P = 0.014）。在PD-L1阳性临界值为1%（OR：0.35，95%CI：0.22 - 0.55，P = 0.000）和50%（OR：0.33，95%CI：0.14 - 0.81，P = 0.015）、老年年龄组（OR：0.56，95%CI：0.35 - 0.89，P = 0.013）、女性占主导的组（OR：0.55，95%CI：0.29 - 0.94，P = 0.030）和吸烟者占主导的组中也发现了负相关。在不同间变性淋巴瘤激酶（ALK）、B-Raf原癌基因（BRAF）、人表皮生长因子受体2（HER2）、磷脂酰肌醇-4,5-二磷酸3-激酶催化亚基α（PIK3CA）状态及间质表皮转化因子（MET）表达水平的患者中，未观察到PD-L1表达有显著差异。在具有KRAS突变的肿瘤中发现PD-L1水平较高（OR：1.45，95%CI：1.18 - 1.80，P = 0.001）。三重（EGFR/ALK/KRAS）野生型非小细胞肺癌与具有EGFR/ALK/KRAS突变的非小细胞肺癌之间的PD-L1表达水平无显著差异。