胶质母细胞瘤（GBM）是最具侵袭性、恶性和耐药性的脑肿瘤。目前正调查针对程序性细胞死亡蛋白1（PD-1）/程序性死亡配体（PD-L1）轴的阻断疗法，以用于GBM的临床管理。本研究以巴基斯坦成年胶质母细胞瘤患者（n = 128）和与之年龄和性别相匹配的健康对照组为对象，量化了手术前血浆PD-L1水平作为GBM的临床管理生物标志物。使用PD-L1铂酶联免疫测定和定量实时PCR测量PD-L1蛋白质和mRNA。采用受试者工作特征（ROC）曲线分析计算特异性和敏感性分析的曲线下面积（AUC）。采用Kaplan-Meier生存分析计算总生存期。PD-L1蛋白质和mRNA在GBM中显著高于健康对照组（p < 0.0001）。GBM的平均PD-L1浓度为48.98 ± 2.290 pg/ml，而对照组为27.63 ± 1.281 pg/ml。基因表达分析显示，在GBM患者血液中PD-L1的上调表达明显（p < 0.0001）。血浆PD-L1的AUC为0.840（p < 0.0001；95% CI = 0.7716 to 0.9090），当截断值高于46 pg/ml时，特异性为100%，敏感性为57.81%。较高的手术前PD-L1水平与总体不良生存有关（p < 0.0001；HR（log-rank）= 0.08；95% CI = 0.04 to 0.15）。年龄、性别和民族背景与血浆PD-L1水平无关。研究总结，GBM中基于血浆PD-L1的测量可以成为有前途的预后标志物和治疗靶点，同时是一种快速且相对非侵入性的例行临床管理筛查工具。将来需要通过涉及预处理和后处理组的多中心协作，扩大对更大队列的分析，以充分探索循环PD-L1在临床应用中的实用性。 版权所有 © 2023 Masood，Batool，Bhatti，Ali，Valko，Jomova和Kuca。

Glioblastoma multiforme (GBM) is the most aggressive, malignant, and therapy-resistant tumor of the brain. Blockade therapy targeting the programmed cell death protein 1 (PD-1)/programmed death ligand (PD-L1) axis is currently under investigation for the clinical management of the GBM. This study has quantified the plasma levels of PD-L1 as a biomarker for the clinical management of GBM.A cohort (n = 128) of Pakistani adult glioblastoma patients together with age- and sex-matched healthy controls was used for quantification of pre-surgery levels of plasma PD-L1. PD-L1 protein and mRNA were measured by PD-L1 platinum enzyme-linked immunosorbent assay and quantitative real-time PCR, respectively. Receiver operating characteristic (ROC) curve analysis was used to compute area under the curve (AUC) for specificity and sensitivity analyses. The Kaplan-Meier survival analysis was employed to compute overall survival.PD-L1 protein and mRNA were significantly higher in GBM compared to the healthy controls (p < 0.0001). Mean PD-L1 concentration for the GBM was found to be 48.98 ± 2.290 pg/ml compared to 27.63 ± 1.281 pg/ml for controls. Gene expression analysis showed statistically significant upregulation (p < 0.0001) of PD-L1 in blood of GBM compared to healthy controls. Plasma PD-L1 showed an AUC of 0.840 (p < 0.0001; 95% CI = 0.7716 to 0.9090) where a cutoff value higher than 46 pg/ml demonstrated 100% specificity and 57.81% sensitivity. Higher pre-surgery levels of PD-L1 were found to be associated with overall poor survival [p < 0.0001; HR (log-rank) = 0.08; 95% CI = 0.04 to 0.15]. Age, gender, and ethnic background were not found to be associated with plasma PD-L1 levels.The study concludes that blood-based measurements of PD-L1 in GBM can be a promising prognostic marker and therapeutic target besides a rapid and relatively non-invasive screening tool for routine clinical management. Future work extending the analysis to larger cohorts through multi-center collaborations involving pre-treatment and post-treatment groups is required to fully explore the usefulness of circulating PD-L1 for effective clinical applications.Copyright © 2023 Masood, Batool, Bhatti, Ali, Valko, Jomova and Kuca.