程序性细胞死亡配体-1表达在乳腺癌预后和总生存中的作用：一项系统评价和荟萃分析。
Role of programmed cell death ligand-1 expression on prognostic and overall survival of breast cancer: A systematic review and meta-analysis.
作者信息
Li Shichao, Chen Li, Jiang Jun
机构信息
Breast Disease Center, Southwest Hospital, Third Military Medical University, Chongqing, China.
出版信息
Medicine (Baltimore). 2019 Apr;98(16):e15201. doi: 10.1097/MD.0000000000015201.
BACKGROUND
Recently, the correlation of immunological checkpoint marker programmed cell death ligand-1 (PD-L1) and the prognosis of various cancers has been a research hotspot. The aim of this study is to examine the prognostic effect of PD-L1 in breast cancer.
METHODS
PubMed, EMBASE, Web of Science, the Cochrane Library database were searched for eligible studies and additional hand-searching were reviewed as an augmentation. Pooled hazard ratios (HR) and 95% confidence interval (CI) for overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS)/recurrence-free survival (RFS), and metastasis-free survival (MFS) were estimated using fixed- or random-effect models.
RESULTS
Data from 19 studies involving 12,505 patients were collected. Study quality was assessed according to guidelines for assessing quality in prognostic studies. PD-L1 expression was significantly associated with lymph node metastasis (P < .001), high tumor grade (P < .001), negative hormone receptor (P < .001), human epidermal growth factor receptor 2 (HER2) positivity (P < .001), high Ki67 (P < .001), and high tumor-infiltrating lymphocytes (TILs) (P < .001). PD-L1 expression had no significant impact on CSS (pooled HR 0.83, 95% CI = 0.64-1.09, P = .19) or MFS (pooled HR 1.11, 95% CI = 0.62-1.97, P = .72), but significantly correlated with shortened OS (pooled HR 1.52, 95% CI = 1.14-2.03, P = .004) and DFS (pooled HR 1.31, 95% CI = 1.14-1.51, P < .000). Subgroup analysis showed that not PD-L1 RNA expression, but protein expression was associated with shorter survival, in addition, the adverse prognostic effect of PD-L1 expression remained in luminal A, luminal B, and HER2 subtype, not in basal-like or triple-negative subtype.
CONCLUSIONS
An elevated PD-L1 expression significantly correlates with high-risk prognostic indicators and decreased survival in patients with breast cancer.
背景
近年来，免疫检查点标志物程序性细胞死亡配体-1（PD-L1）与各种癌症预后的相关性一直是研究热点。本研究旨在探讨PD-L1在乳腺癌中的预后作用。
方法
检索PubMed、EMBASE、Web of Science、Cochrane图书馆数据库以获取符合条件的研究，并进行额外的手工检索作为补充。使用固定效应或随机效应模型估计总生存期（OS）、癌症特异性生存期（CSS）、无病生存期（DFS）/无复发生存期（RFS）和无转移生存期（MFS）的合并风险比（HR）及95%置信区间（CI）。
结果
收集了19项研究中12505例患者的数据。根据预后研究质量评估指南对研究质量进行评估。PD-L1表达与淋巴结转移（P<0.001）、高肿瘤分级（P<0.001）、激素受体阴性（P<0.001）、人表皮生长因子受体2（HER2）阳性（P<0.001）、高Ki67（P<0.001）及高肿瘤浸润淋巴细胞（TILs）（P<0.001）显著相关。PD-L1表达对CSS（合并HR 0.83，95%CI=0.64-1.09，P=0.19）或MFS（合并HR 1.11，95%CI=0.62-1.97，P=0.72）无显著影响，但与OS缩短（合并HR 1.52，95%CI=1.14-2.03，P=0.004）和DFS（合并HR 1.31，95%CI=1.14-1.51，P<0.000）显著相关。亚组分析显示，与生存期缩短相关的不是PD-L1 RNA表达，而是蛋白表达，此外，PD-L1表达的不良预后作用在腔面A型、腔面B型和HER2亚型中存在，在基底样或三阴性亚型中不存在。
结论
PD-L1表达升高与乳腺癌患者的高危预后指标及生存期缩短显著相关。
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