非小细胞肺癌放疗后 PD-1/sPD-L1 免疫指标表达变化的分子机制。
Molecular Mechanism of Expression Changes of Immunological Indexes of PD-1/sPD-L1 after Radiotherapy in Nonsmall Cell Lung Cancer.
机构信息
Department of Radiation Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang 110042, China.
出版信息
Biomed Res Int. 2021 Apr 20;2021:8811751. doi: 10.1155/2021/8811751. eCollection 2021.
It is aimed at investigating the changes of serum soluble programmed death-ligand 1 (sPD-L1) expression level in nonsmall cell lung cancer (NSCLC) before and after radiotherapy, the correlation of PD-L1, PD-1, and proteins of Akt (protein kinase B), mTOR, and HIF-1, and the molecular mechanism of the PD-1/PD-L1 pathway in the development of NSCLS. A total of 126 NSCLC patients receiving radiotherapy in Liaoning Cancer Hospital from September 2018 to September 2019 were selected as the observation group, and another 58 healthy volunteers were selected as the control group. NSCLC patients were divided into group A (stage I-II, stereotactic radiotherapy) and group B (stage III, intensity-modulated radiation therapy) according to the cancer stage. The efficacy of radiotherapy was evaluated, and sPD-L1 expression was detected by ELISA. The immunohistochemical staining was adopted to detect protein expressions of Akt, mTOR, and HIF-1 in NSCLC tissues. The correlation between their expression and expression of PD-L1 and PD-1 was analyzed. The results showed that the overall response rate (ORR) of group A was 89.29%, the clinical benefit response (CBR) was 96.43%, the median survival time (MST) was 25 months, and the survival rate within three years was 72.56%. In group B, the ORR was 70.41%, the CBR was 97.96%, the MST was 18 months, and the survival rate within three years was 34.67%. Comparison of overall serum sPD-L1 expression in the control group, group A, and group B and between groups before radiotherapy was statistically significant ( < 0.01). After radiotherapy, serum sPD-L1 expression in group A and group B decreased compared with that before radiotherapy ( < 0.01). Among NSCLC patients, the positive expression rate of Akt, mTOR, and HIF-1 was 71.32%, 41.26%, and 80.65%, respectively. PD-L1 expression and Akt, mTOR, and HIF-1 expression showed a significant correlation. PD1 expression and Akt, mTOR, and HIF-1 expression also showed a significant correlation. It indicated that the expression level of sPD-L1 in NSCLC patients was higher than that in normal subjects, but the expression level of sPD-L1 was decreased after radiotherapy. PD-1/PD-L1 may play important roles in NSCLC procession through the Akt/mTOR and HIF-1 pathway.
本研究旨在探讨非小细胞肺癌（NSCLC）患者放疗前后血清可溶性程序性死亡配体 1（sPD-L1）表达水平的变化，分析 PD-L1、PD-1 与 Akt（蛋白激酶 B）、mTOR、HIF-1 蛋白的相关性，以及 PD-1/PD-L1 通路在 NSCLC 发生、发展中的分子机制。选取 2018 年 9 月至 2019 年 9 月在辽宁省肿瘤医院接受放疗的 NSCLC 患者 126 例作为观察组，另选取同期 58 例健康志愿者作为对照组。根据肿瘤分期，将 NSCLC 患者分为 A 组（Ⅰ-Ⅱ期，立体定向放疗）和 B 组（Ⅲ期，调强放疗）。评价放疗疗效，采用 ELISA 法检测 sPD-L1 表达，免疫组化法检测 NSCLC 组织中 Akt、mTOR、HIF-1 蛋白表达，分析其与 PD-L1、PD-1 表达的相关性。结果显示，A 组总有效率（ORR）为 89.29%，临床获益反应（CBR）为 96.43%，中位生存时间（MST）为 25 个月，3 年生存率为 72.56%；B 组 ORR 为 70.41%，CBR 为 97.96%，MST 为 18 个月，3 年生存率为 34.67%。对照组、A 组、B 组患者放疗前、后总体血清 sPD-L1 表达比较，差异均有统计学意义（ < 0.01）。放疗后 A 组、B 组患者血清 sPD-L1 表达均低于放疗前（ < 0.01）。NSCLC 患者中 Akt、mTOR、HIF-1 阳性表达率分别为 71.32%、41.26%、80.65%，PD-L1 表达与 Akt、mTOR、HIF-1 表达呈显著正相关，PD-1 表达与 Akt、mTOR、HIF-1 表达也呈显著正相关。结果表明，NSCLC 患者 sPD-L1 表达水平高于正常人群，但放疗后 sPD-L1 表达水平降低。PD-1/PD-L1 可能通过 Akt/mTOR 和 HIF-1 通路在 NSCLC 进程中发挥重要作用。
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