Comprehensive Oncogenic Features of Coronavirus Receptors in Glioblastoma Multiforme

Abstract

The COVID-19 pandemic caused by SARS-CoV-2 infection has placed health systems under excessive pressure and especially elderly people with cancer. Glioblastoma multiforme (GBM) is a malignant brain tumor with an increasing incidence in elderly individuals, and thereby GBM patients are a vulnerable population during the COVID-19 outbreak. Accumulating studies have implied that SARS-CoV-2 might invade the brain directly via coronavirus receptors. However, little is known about SARS-CoV-2 infection in the clinical development of GBM. Here, we explored the oncogenic roles of six coronavirus receptors (ACE2, DPP4, ANPEP, AXL, TMPRSS2, and ENPEP) in GBM using bioinformatics and experimental approaches. We found that ANPEP and ENPEP were significantly increased at both the mRNA and protein levels in GBM compared with normal brain tissue. Kaplan–Meier survival curves and Cox regression analysis demonstrated that high expressions of ANPEP and ENPEP are associated with poor prognosis and survival. Moreover, all receptors are positively correlated with the immune infiltration levels of monocyte. Furthermore, we identified 245 genes between COVID-19 and coronavirus receptors–correlated genes in GBM and performed a thorough analysis of their protein–protein interaction network, functional signaling pathway and molecular process. Our work explores for the first time the association of coronavirus receptors with GBM and suggests ANPEP and ENPEP as potential therapeutic targets of GBM irrespective of COVID-19.

Evaluating glioblastoma tumour sphere growth and migration in interaction with astrocytes using 3D collagen-hyaluronic acid hydrogels

“…Of the six genes highlighted by our study, CA9 and FPR1 are associated with increased invasion through STAT3 signalling, 44,45 and TMRPSS2 is associated with invasion through the HGF/MET nexus. 46,49,50 The remaining genes, HLA-DQA1, KLRD1, and OAS2, are associated with immune response. 53,54,58 Thus STAT3 and HGF/MET signalling likely mediate observed differences in cell migration.…”

“…We first compared LN229 to U87 samples in mono-culture without astrocyte and co-culture with astrocytes to identify differences between cell lines (Table 1 [44][45][46][47][48][49][50][51][52][53][54][55][56][57][58] ). In co-culture, 31 genes were differentially expressed genes (DEGs) with a log fold change (FC) 42 and a p value o0.05 (Table S2 and Fig.…”

“…To identify differences resulting specifically from cross-talk as opposed to the presence of astrocytes alone, we also compared each GB co-culture to a sample comprised of mixed RNA from GB cells and astrocytes grown separately (Table 2 44,45,49,50,53,54,[58][59][60][61][62][63][64][65][66][67][68][69][70][71][72] ). Co-cultures vs. mixed separate culture comparisons for LN229 and U87 cells yielded 55 and 58 DEGs, respectively (Tables S4, S5 and Fig.…”

SARS-CoV-2 and cancer: the intriguing and informative cross-talk

“…Moreover, all receptors are positively correlated with the immune infiltration levels of monocytes. Interestingly, Chen et al (2022) explored the association of coronavirus receptors with GBM and suggested ANPEP and ENPEP as potential therapeutic targets of GBM irrespective of COVID-19 [37] .…”

SARS-CoV-2 Pattern Provides a New Scoring System and Predicts the Prognosis and Immune Therapeutic Response in Glioma

“…Wang et al showed that high expression of C1R, chemokine (C-C-motif) ligand 2 (CCL2), and TNF receptor superfamily 1A (TNFRSF1A) in the COVID-19 pathway was significantly associated with low survival in GBM patients and immune cell infiltration, which may be used as molecular biomarkers of prognosis and immune infiltration in patients with GBM in the future [ 15 ]. Chen’s team also found that, compared with normal brain tissue, viral receptors Alanyl aminopeptidase (ANPEP) and Glutamyl Aminopeptidase (ENPEP) were significantly increased in both mRNA and protein levels in GBM and were associated with poor prognosis and survival [ 16 ]. These studies provide valuable entry points for the further exploration of the correlation between COVID-19 and glioma.…”