TY - JOUR

T1 - uPAR (PLAUR) Marks Two Intra-Tumoral Subtypes of Glioblastoma

T2 - Insights from Single-Cell RNA Sequencing

AU - He, Yue

AU - Døssing, Kristina B.V.

AU - Rossing, Maria

AU - Bagger, Frederik Otzen

AU - Kjaer, Andreas

N1 - Publisher Copyright: © 2024 by the authors.

PY - 2024

Y1 - 2024

N2 - Urokinase plasminogen activator receptor (uPAR) encoded by the PLAUR gene is known as a clinical marker for cell invasiveness in glioblastoma multiforme (GBM). It is additionally implicated in various processes, including angiogenesis and inflammation within the tumor microenvironment. However, there has not been a comprehensive study that depicts the overall functions and molecular cooperators of PLAUR with respect to intra-tumoral subtypes of GBM. Using single-cell RNA sequencing data from 37 GBM patients, we identified PLAUR as a marker gene for two distinct subtypes in GBM. One subtype is featured by inflammatory activities and the other subtype is marked by ECM remodeling processes. Using the whole-transcriptome data from single cells, we are able to uncover the molecular cooperators of PLAUR for both subtypes without presuming biological pathways. Two protein networks comprise the molecular context of PLAUR, with each of the two subtypes characterized by a different dominant network. We concluded that targeting PLAUR directly influences the mechanisms represented by these two protein networks, regardless of the subtype of the targeted cell.

AB - Urokinase plasminogen activator receptor (uPAR) encoded by the PLAUR gene is known as a clinical marker for cell invasiveness in glioblastoma multiforme (GBM). It is additionally implicated in various processes, including angiogenesis and inflammation within the tumor microenvironment. However, there has not been a comprehensive study that depicts the overall functions and molecular cooperators of PLAUR with respect to intra-tumoral subtypes of GBM. Using single-cell RNA sequencing data from 37 GBM patients, we identified PLAUR as a marker gene for two distinct subtypes in GBM. One subtype is featured by inflammatory activities and the other subtype is marked by ECM remodeling processes. Using the whole-transcriptome data from single cells, we are able to uncover the molecular cooperators of PLAUR for both subtypes without presuming biological pathways. Two protein networks comprise the molecular context of PLAUR, with each of the two subtypes characterized by a different dominant network. We concluded that targeting PLAUR directly influences the mechanisms represented by these two protein networks, regardless of the subtype of the targeted cell.

KW - CD44

KW - ECM degradation

KW - FN1

KW - GBM cell invasiveness

KW - inflammatory microenvironment

KW - PLAUR

KW - single-cell RNA sequencing

KW - uPAR

U2 - 10.3390/ijms25041998

DO - 10.3390/ijms25041998

M3 - Journal article

C2 - 38396677

AN - SCOPUS:85185974931

VL - 25

JO - International Journal of Molecular Sciences (Online)

JF - International Journal of Molecular Sciences (Online)

SN - 1661-6596

IS - 4

M1 - 1998

ER -