Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.
Department of Gastroenterological and Pediatric Surgery, Oita University Faculty of Medicine, Yufu, Japan.
Ann Surg Oncol. 2020 Oct;27(10):4035-4043. doi: 10.1245/s10434-020-08375-z. Epub 2020 Mar 21.
Programmed cell death 1 (PD-1) inhibitors have shown significant therapeutic promise in various cancers. However, the clinical significance of PD-1 expression remains not fully understood. In this study, we evaluated the clinical and prognostic relevance of PD-1 expression in breast cancer (BC).
First, we analyzed PD-1 mRNA expression in BC tissues and performed a survival analysis using a dataset from The Cancer Genome Atlas. Next, we measured PD-1 mRNA expression in peripheral blood (PB) in BC patients by quantitative reverse-transcription polymerase chain reaction. We performed a survival analysis and evaluated the association between PD-1 mRNA expression in PB and the clinicopathological features of 372 BC patients who underwent curative resection. Flow cytometry (FCM) analysis was performed to identify PD-1-expressing cells in PB. Finally, we determined whether there was a correlation of PD-1 mRNA expression in PB and tumor tissue.
PD-1 mRNA expression was significantly higher in tumor tissues compared with normal tissues. Decreased PD-1 mRNA expression in tumor tissue was associated with poor overall survival (OS). PD-1 mRNA expression in PB of BC patients was higher than that of healthy volunteers, and increased PD-1 mRNA expression in PB was associated with poor OS. FCM revealed that PD-1 was mostly expressed on T cells in PB, predominantly in CD4 T cells. PD-1 mRNA expression in PB was negatively correlated with PD-1 mRNA expression in tumor tissue.
High expression of PD-1 mRNA in preoperative PB could serve as an effective biomarker that indicates poor prognosis in BC.
程序性细胞死亡蛋白 1(PD-1)抑制剂在多种癌症中显示出显著的治疗潜力。然而,PD-1 表达的临床意义仍不完全清楚。在这项研究中,我们评估了 PD-1 表达在乳腺癌(BC)中的临床和预后相关性。
首先,我们分析了 BC 组织中 PD-1 mRNA 的表达,并使用来自癌症基因组图谱的数据集进行了生存分析。接下来,我们通过定量逆转录聚合酶链反应测量了 BC 患者外周血(PB)中的 PD-1 mRNA 表达。我们进行了生存分析,并评估了 372 例接受根治性切除的 BC 患者 PB 中 PD-1 mRNA 表达与临床病理特征之间的关系。进行了流式细胞术(FCM)分析以鉴定 PB 中表达 PD-1 的细胞。最后,我们确定了 PB 中 PD-1 mRNA 表达与肿瘤组织之间是否存在相关性。
肿瘤组织中 PD-1 mRNA 的表达明显高于正常组织。肿瘤组织中 PD-1 mRNA 表达降低与总生存期(OS)不良相关。BC 患者 PB 中的 PD-1 mRNA 表达高于健康志愿者,并且 PB 中 PD-1 mRNA 表达增加与 OS 不良相关。FCM 显示 PB 中的 PD-1 主要在 T 细胞上表达,主要在 CD4 T 细胞上表达。PB 中的 PD-1 mRNA 表达与肿瘤组织中的 PD-1 mRNA 表达呈负相关。
术前 PB 中 PD-1 mRNA 的高表达可作为预示 BC 预后不良的有效生物标志物。