原发性乳腺癌中程序性细胞死亡受体 1（PD-1）和程序性死亡配体 1（PD-L1）基因的表达。
Programmed cell death 1 (PD-1) receptor and programmed death ligand 1 (PD-L1) gene expression in primary breast cancer.
机构信息
Massachusetts General Hospital, 55 Fruit Street, Bartlett Hall Extension 1-213, Boston, MA, 02114, USA.
University of California San Francisco, San Francisco, CA, USA.
出版信息
Breast Cancer Res Treat. 2021 Jun;187(2):387-395. doi: 10.1007/s10549-021-06234-3. Epub 2021 Apr 28.
PURPOSE
The interaction of the programmed cell death 1 (PD-1) receptor on tumor-infiltrating lymphocytes with programmed death ligand 1 (PD-L1) on tumor cells downregulates anti-tumor immunity. This study evaluated associations between PD-1 and PD-L1 expression in primary breast cancer, clinical characteristics, and patient outcomes.
METHODS
Microarray data from the Investigation of Serial Studies to predict your therapeutic response with imaging and molecular analysis (I-SPY 1) study (n = 149) was used to evaluate PD-1 and PD-L1 expression. Associations with clinical features and chemotherapy response were determined using Kruskal-Wallis and Wilcoxon rank sum tests, respectively. Recurrence-free survival (RFS) associations were determined with the Cox proportional hazard model. Associations of PD-1 and PD-L1 and selected genes associated with breast cancer, as well as a predictor of olaparib response (PARPi-7), were determined in I-SPY 1 and 2 other datasets: METABRIC (n = 1992) and TCGA (n = 817), using Pearson correlations.
RESULTS
In I-SPY 1, PD-1 expression was higher in triple-negative breast cancer (TNBC) and HER2 + breast cancer (p = 0.003), and grade 2/3 tumors (p = 0.043), and was associated with pathologic complete response (p = 0.006). PD-L1 expression in the lowest quintile was associated with worse RFS, even after subtype adjustment (HR 2.33, p = 0.01). PD-1 and PD-L1 gene expression correlated with the expression of immune-related genes and PARPi-7.
CONCLUSIONS
PD-1 expression is higher in breast cancers with aggressive features such as TNBC. Low PD-L1 expression may be an adverse prognostic factor. PD-1 and PD-L1 gene expression correlates with the expression of immune-related and DNA damage repair genes.
目的
肿瘤浸润淋巴细胞上的程序性细胞死亡 1（PD-1）受体与肿瘤细胞上的程序性死亡配体 1（PD-L1）相互作用，下调抗肿瘤免疫。本研究评估了原发性乳腺癌中 PD-1 和 PD-L1 表达与临床特征和患者结局的相关性。
方法
利用 Investigation of Serial Studies to predict your therapeutic response with imaging and molecular analysis（I-SPY 1）研究的微阵列数据（n=149）评估 PD-1 和 PD-L1 的表达。使用 Kruskal-Wallis 和 Wilcoxon 秩和检验分别确定与临床特征和化疗反应的相关性。使用 Cox 比例风险模型确定无复发生存（RFS）相关性。使用 Pearson 相关性在 I-SPY 1 和另外 2 个数据集（METABRIC，n=1992；TCGA，n=817）中确定 PD-1 和 PD-L1 与乳腺癌相关的选定基因以及奥拉帕利反应（PARPi-7）预测因子的相关性。
结果
在 I-SPY 1 中，三阴性乳腺癌（TNBC）和 HER2+乳腺癌（p=0.003）和 2/3 级肿瘤（p=0.043）中 PD-1 的表达更高，并且与病理完全缓解（p=0.006）相关。最低五分位数的 PD-L1 表达与 RFS 较差相关，即使在亚型调整后（HR 2.33，p=0.01）。PD-1 和 PD-L1 基因表达与免疫相关基因和 PARPi-7 的表达相关。
结论
PD-1 的表达在具有侵袭性特征的乳腺癌（如 TNBC）中更高。低 PD-L1 表达可能是预后不良的因素。PD-1 和 PD-L1 基因表达与免疫相关和 DNA 损伤修复基因的表达相关。
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