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分析根治性调强放疗后鼻咽癌患者血浆 EBV-DNA 和可溶性检查点蛋白。

Analysis of Plasma EBV-DNA and Soluble Checkpoint Proteins in Nasopharyngeal Carcinoma Patients after Definitive Intensity-Modulated Radiotherapy.

机构信息

Precision Medicine Center, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, China.

Department of Radiotherapy, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, China.

出版信息

Biomed Res Int. 2019 May 5;2019:3939720. doi: 10.1155/2019/3939720. eCollection 2019.

Abstract

BACKGROUND

Tumor immunotherapy and immunological checkpoint-related proteins are research hotspots. Intensity-modulated radiotherapy (IMRT) is the main treatment for nasopharyngeal carcinoma (NPC). Hence, the evaluation of its effect is very important. The aim of this study was to assess the relationship between the concentrations of soluble checkpoint proteins, plasma EBV-DNA, and cytokines in NPC patients treated with IMRT.

METHODS

In this study, the plasma samples of 37 NPC patients and 40 healthy controls were collected. Luminex MAGPIX was used to detect the concentrations of 32 plasma targets, including soluble programmed cell death 1 (sPD-1). RT-qPCR was used to measure EBV-DNA.

RESULTS

The concentrations of 33 plasma targets were detected in NPC patients before and after IMRT to explore the changes after IMRT. The results showed that IMRT could increase the expression of sPD-1 and significantly reduce the level of EBV-DNA in the plasma of NPC patients. The expression level of sPD-1 in TNM I/II patients was significantly higher than that in III/IV patients. Besides, the concentrations of 12 other targets were significantly different after IMRT, including LAG-3, PD-L1, TIM-3, IFN-, IL-12p70, IL-1, IL-5, IL-6, TNF-, IL-10, IL-17A, and IL-22. High sPD-1 patients had longer survival than those with low sPD-1. Also, patients with lower EBV-DNA and TNM grades I and II/III had longer survival than those with higher EBV-DNA or TNM IV.

CONCLUSIONS

This study demonstrated that the concentration of sPD-1 was significantly increased and EBV-DNA was significantly reduced in the NPC patients after IMRT. Plasma EBV-DNA level was a highly specific and sensitive biomarker for NPC diagnosis. Both sPD-1 expression and EBV-DNA concentration in plasma were related to the survival of patients.

摘要

背景

肿瘤免疫治疗和免疫检查点相关蛋白是研究热点。调强放疗(IMRT)是鼻咽癌(NPC)的主要治疗方法。因此,评估其疗效非常重要。本研究旨在评估 NPC 患者接受 IMRT 治疗后可溶性检查点蛋白、血浆 EBV-DNA 和细胞因子浓度之间的关系。

方法

本研究收集了 37 例 NPC 患者和 40 例健康对照者的血浆样本。采用 Luminex MAGPIX 检测 32 种血浆靶标(包括可溶性程序性死亡 1(sPD-1))的浓度。采用 RT-qPCR 测量 EBV-DNA。

结果

在接受 IMRT 前后检测 NPC 患者的 33 种血浆靶标浓度,以探讨 IMRT 后的变化。结果表明,IMRT 可增加 sPD-1 的表达,并显著降低 NPC 患者血浆中 EBV-DNA 的水平。TNM I/II 期患者的 sPD-1 表达水平明显高于 III/IV 期患者。此外,IMRT 后 12 种其他靶标的浓度差异有统计学意义,包括 LAG-3、PD-L1、TIM-3、IFN-γ、IL-12p70、IL-1、IL-5、IL-6、TNF-α、IL-10、IL-17A 和 IL-22。高 sPD-1 患者的生存时间长于低 sPD-1 患者。此外,EBV-DNA 水平较低且 TNM 分期为 I 期和 II/III 期的患者的生存时间长于 EBV-DNA 水平较高或 TNM 分期为 IV 期的患者。

结论

本研究表明,NPC 患者接受 IMRT 治疗后 sPD-1 浓度明显升高,EBV-DNA 明显降低。血浆 EBV-DNA 水平是 NPC 诊断的高度特异和敏感的生物标志物。sPD-1 表达和血浆 EBV-DNA 浓度均与患者的生存相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4bbc/6525834/1c0d9dd4c216/BMRI2019-3939720.001.jpg

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