A radiosensitivity gene signature and PD-L1 status predict clinical outcome of patients with invasive breast carcinoma in The Cancer Genome Atlas (TCGA) dataset
A radiosensitivity gene signature and PD-L1 status predict clinical outcome of patients with invasive breast carcinoma in The Cancer Genome Atlas (TCGA) dataset
复制标题
DOI：
10.1016/j.radonc.2017.05.009
复制
发表时间：
2017-09-01
影响因子：
5.7
通讯作者：
Kim, In Ah
中科院分区：
文献类型：
--
作者：
Jang, Bum-Sup;Kim, In Ah
背景和目的：我们研究了放射敏感性基因标记与程序性细胞死亡配体1 （PD-L1）状态和临床结果之间的联系，以确定一组可能从放射治疗（RT）联合抗pd1 /PD-L1治疗中获益的患者。材料和方法：我们在癌症基因组图谱（TCGA）数据集中验证了鉴定的与放射敏感性相关的基因特征，并分析了浸润性乳腺癌的PD-L1状态。为了验证基因标记，选择1045例患者，并根据其预后根据其放射敏感（RS）或放射耐药（RR）命名，使用共识聚类算法将其分为两类。根据CD274 mRNA表达水平的中位数作为PD-L1的替代品，将患者分层为PD-L1高或PD-L1低。结果：单因素分析显示，仅在接受rt治疗时，RS组患者的无复发生存（RFS）风险低于RR组（HR 0.45, 95% CI 0.25-0.81, p = 0.008）。RS组与pd - l1高水平组独立相关，且RS组CD274 mRNA表达显著高于RR组（p < 0.001）。多因素分析显示，pd - l1高组与RR组相比，RS组有更好的RFS （HR 0.37, 95% CI 0.16-0.87, p = 0.022）。PD-L1表达水平可能代表肿瘤的免疫原性，因此，我们推测PD-L1高组有更多的免疫原性肿瘤，可能对辐射诱导的免疫细胞死亡更敏感。结论：我们首先评估了放射敏感性基因标记的预测价值，并描述了该放射敏感性基因标记与PD-L1之间的关系。放射敏感性基因标记和PD-L1状态是预测浸润性乳腺癌患者RT治疗临床结果的重要因素，可用于选择RT联合抗pd1 /PDL1治疗的受益患者。(C) 2017 Elsevier B.V.版权所有
Background and purpose: We investigated the link between the radiosensitivity gene signature and programmed cell death ligand 1 (PD-L1) status and clinical outcome in order to identify a group of patients that would possibly receive clinical benefit of radiotherapy (RT) combined with anti-PD1/PD-L1 therapy.Material and methods: We validated the identified gene signature related to radiosensitivity and analyzed the PD-L1 status of invasive breast cancer in The Cancer Genome Atlas (TCGA) dataset. To validate the gene signature, 1045 patients were selected and divided into two clusters using a consensus clustering algorithm based on their radiosensitive (RS) or radioresistant (RR) designation according to their prognosis. Patients were also stratified as PD-L1-high or PD-L1-low based on the median value of CD274 mRNA expression level as surrogates of PD-L1.Results: Patents assigned to the RS group had decreased risk of recurrence-free survival (RFS) rate than patients in the RR group by univariate analysis (HR 0.45, 95% CI 0.25-0.81, p = 0.008) only when treated with RT. The RS group was independently associated with the PD-L1-high group, and CD274 mRNA expression was significantly higher in the RS group (p < 0.001) than the RR group. In the PD-L1-high group, the RS group was associated with better RFS compared to the RR group (HR 0.37, 95% CI 0.16-0.87, p = 0.022) in multivariate analysis. The level of PD-L1 expression may represent the immunogenicity of tumors, and thus, we speculated that the PD-L1-high group had more immunogenic tumors, which could be more sensitive to radiation-induced immunologic cell death.Conclusion: We first evaluated the predictive value of the radiosensitivity gene signature and described a relationship with this radiosensitivity gene signature and PD-L1. The radiosensitivity gene signature and PD-L1 status were important factors for prediction of the clinical outcome of RT in patients with invasive breast cancer and may be used for selecting patients who will benefit from RT combined with anti-PD1/PDL1 therapy. (C) 2017 Elsevier B.V. All rights reserved.