Plasma PD-L1 as a biomarker in the clinical management of glioblastoma multiforme-a retrospective cohort study

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00179906%3A_____%2F23%3A10469229" target="_blank" >RIV/00179906:_____/23:10469229 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/62690094:18470/23:50020568

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=xc-28HCydS" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=xc-28HCydS</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fimmu.2023.1202098" target="_blank" >10.3389/fimmu.2023.1202098</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Plasma PD-L1 as a biomarker in the clinical management of glioblastoma multiforme-a retrospective cohort study

Popis výsledku v původním jazyce

Background and objectivesGlioblastoma 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. MethodsA 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. ResultsPD-L1 protein and mRNA were significantly higher in GBM compared to the healthy controls (p &lt; 0.0001). Mean PD-L1 concentration for the GBM was found to be 48.98 &amp; PLUSMN; 2.290 pg/ml compared to 27.63 &amp; PLUSMN; 1.281 pg/ml for controls. Gene expression analysis showed statistically significant upregulation (p &lt; 0.0001) of PD-L1 in blood of GBM compared to healthy controls. Plasma PD-L1 showed an AUC of 0.840 (p &lt; 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 &lt; 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. ConclusionThe 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.

Název v anglickém jazyce

Plasma PD-L1 as a biomarker in the clinical management of glioblastoma multiforme-a retrospective cohort study

Popis výsledku anglicky

Background and objectivesGlioblastoma 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. MethodsA 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. ResultsPD-L1 protein and mRNA were significantly higher in GBM compared to the healthy controls (p &lt; 0.0001). Mean PD-L1 concentration for the GBM was found to be 48.98 &amp; PLUSMN; 2.290 pg/ml compared to 27.63 &amp; PLUSMN; 1.281 pg/ml for controls. Gene expression analysis showed statistically significant upregulation (p &lt; 0.0001) of PD-L1 in blood of GBM compared to healthy controls. Plasma PD-L1 showed an AUC of 0.840 (p &lt; 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 &lt; 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. ConclusionThe 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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2023

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Frontiers in Immunology

ISSN

1664-3224

e-ISSN

—

Svazek periodika

14

Číslo periodika v rámci svazku

Jul

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

9

Strana od-do

1202098

Kód UT WoS článku

001037044600001

EID výsledku v databázi Scopus

2-s2.0-85166055866