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外周血循环 PD-1 mRNA 是预测乳腺癌患者生存的潜在生物标志物。

Circulating PD-1 mRNA in Peripheral Blood is a Potential Biomarker for Predicting Survival of Breast Cancer Patients.

机构信息

Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.

Department of Gastroenterological and Pediatric Surgery, Oita University Faculty of Medicine, Yufu, Japan.

出版信息

Ann Surg Oncol. 2020 Oct;27(10):4035-4043. doi: 10.1245/s10434-020-08375-z. Epub 2020 Mar 21.

Abstract

BACKGROUND

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).

METHODS

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.

RESULTS

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.

CONCLUSION

High expression of PD-1 mRNA in preoperative PB could serve as an effective biomarker that indicates poor prognosis in BC.

摘要

背景

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。

方法

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。

结果

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。

结论

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。

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