Gene and protein expression of programmed death-ligand 1 (PD-L1) are prognostic in early breast cancer (BC), but their prognostic information is inconsistent at least in some biological subgroups. The validated prognostic gene signatures (GS) in BC are mainly based on proliferation and estrogen receptor (ER)-related genes. Here, we aimed to explore the prognostic capacity of PD-L1 expression at the protein vs mRNA levels and to investigate the prognostic information that PD-L1 can potentially add to routinely used GS. Gene expression data were derived from two early BC cohorts (cohort 1: 562 patients; cohort 2: 1081 patients). Tissue microarrays from cohort 1 were immunohistochemically (IHC) stained for PD-L1 using the SP263 clone. GS scores (21-gene, 70-gene) were calculated, and likelihood-ratio (LR) tests and concordance indices were used to evaluate the additional prognostic information for each signature. The immune cell composition was also evaluated using the CIBERSORT in silico tool. PD-L1 gene and protein expressions were independently associated with better prognosis. In ER+/HER2- patients, PD-L1 gene expression provided significant additional prognostic information beyond that of both 21-GS [LR-Δχ2 = 15.289 and LR-Δχ2 = 8.812, P < 0.01 for distant metastasis-free interval (DMFI) in cohorts 1 and 2, respectively] and 70-GS score alone (LR-Δχ2 = 18.198 and LR-Δχ2 = 8.467, P < 0.01 for DMFI in cohorts 1 and 2, respectively). PD-L1 expression was correlated with IHC-determined CD3+ cells (r = 0.41, P < 0.001) and with CD8+ (r = 0.62, P < 0.001) and CD4+ memory activated (r = 0.66, P < 0.001) but not with memory resting (r = -0.063, P = 0.14) or regulatory (r = -0.12, P < 0.01) T cells in silico. PD-L1 gene expression represents a promising favorable prognostic marker and can provide additional prognostic value to 21- and 70-gene scores in ER+/HER2- BC.

中文翻译：

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程序性死亡配体1基因表达是早期乳腺癌的预后标志物，可为雌激素受体阳性疾病的21个基因和70个基因特征提供更多的预后价值。

程序性死亡配体1（PD-L1）的基因和蛋白质表达在早期乳腺癌（BC）中具有预后性，但至少在某些生物学亚组中它们的预后信息不一致。BC中经过验证的预后基因签名（GS）主要基于增殖和雌激素受体（ER）相关基因。在这里，我们旨在探讨PD-L1在蛋白质与mRNA水平之间表达的预后能力，并研究PD-L1可能增加常规使用的GS的预后信息。基因表达数据来自两个早期的BC队列（队列1：562名患者；队列2：1081名患者）。使用SP263克隆对队列1的组织微阵列进行免疫组织化学（IHC）染色以检测PD-L1。计算了GS得分（21个基因，70个基因），并使用似然比（LR）测试和一致性指数评估每个签名的其他预后信息。还使用CIBERSORT in silico工具评估了免疫细胞组成。PD-L1基因和蛋白质表达与更好的预后独立相关。在ER + / HER2-患者中，PD-L1基因表达提供了21-GS以外的重要预后信息[LR-Δχ2= 15.289和LR-Δχ2= 8.812，对于远处无转移间隔（DMFI），P <0.01队列1和2）和单独的70-GS评分（LR-Δχ2= 18.198和LR-Δχ2= 8.467，DMFI在队列1和2中分别为P <0.01）。PD-L1表达与IHC确定的CD3 +细胞（r = 0.41，P <0.001）和CD8 +（r = 0.62，P <0.001）和CD4 +记忆激活（r = 0.66，P <0）相关。001），但记忆静止（r = -0.063，P = 0.14）或调节性（r = -0.12，P <0.01）的T细胞在计算机上却没有。PD-L1基因表达代表有希望的有利预后标志物，并且可以为ER + / HER2-BC中21和70基因评分提供额外的预后价值。