Table 1 Open in new tab Summary of the...

Source

Isolation method

Identified molecules

Potential clinical Applications

Ref.

Mouse plasma

Differential ultracentrifugation

EGFRvIII

-Diagnosis

²³

-Treatment tailoring/monitoring

-Anti-EGFRvIII treatment

-Vaccine

In vitro(cell lines; GBM stem cells)

Differential ultracentrifugation

CLIC1

-Treatment tailoring

²⁴

In vitro(cell lines), Mouse plasma, Patient’s plasma

Differential ultracentrifugation

Proteins: CAV1, IL8, PDGFs, MMPs, PTX3, CD26, PAI1,
Transcripts: ADM, LOX, IGFPB 3, BCL2, BNIP3, NDRG1, PLOD2, PAI1

-Diagnosis

²⁵

-Treatment tailoring/monitoring

-Assessment of GBM oxygenation status

-Angiogenesis inhibitors

In vitro (GBM stem cells)

Differential ultracentrifugation

miR-148a-3p, miR-9-5p, miR-16-2-3p, miR-182-5p, miR-9-3p, miR-22-3p, miR-186-5p, miR-378e

-Diagnosis

²⁶

-Treatment tailoring/monitoring

-Angiogenesis inhibitors

In vitro (GBM stem cells)

Differential ultracentrifugation

97 mRNAs (RP, OXPHOS, glycolysis)

-Diagnosis

²⁸

-Treatment tailoring/monitoring

In vitro (GBM cell line)

Differential ultracentrifugation

miR-21

-Diagnosis

²⁹

-Treatment tailoring/monitoring

In vitro (GBM stem cells)

Differential ultracentrifugation

miR-451, miR-21, miR-15b, miR-146a, miR-223

-Diagnosis

³⁰

-Treatment tailoring/monitoring

In vitro (GBM stem cells)

Differential ultracentrifugation

Proteins involved in leukocyte recruitment and focal adhesion mechanisms

-Treatment tailoring/monitoring

³¹

-Agents blocking CSF-1R

Patients’ serum

Differential ultracentrifugation

EGFR, EGFRvIII, and TGF-β

-Diagnosis

³³

-Treatment tailoring/monitoring

-Anti-EGFRvIII treatment

-Vaccine

In vitro(cell lines)

Differential ultracentrifugation

HSPs 90, 70, 60, and 27

-Diagnosis

³⁴

-Treatment tailoring/monitoring

-Vaccine

In vitro (GBM stem cells)

Differential ultracentrifugation

PD-L1 (protein and DNA)

-Diagnosis

³⁵

-Treatment tailoring/monitoring

Patients’ serum/plasma

-anti-PD1 receptor blocking antibody

-Tumor subtyping

Patients CSF

Differential ultracentrifugation

wtEGFR RNA, EGFRvIII RNA

-Diagnosis

³⁷

-Treatment tailoring/monitoring

-Anti-EGFRvIII treatment

-Vaccine

In vitro (GBM stem cells), Mouse serum, Patients’ serum

Differential ultracentrifugation

Sema3A

-Diagnosis

⁴⁰

-Treatment tailoring

-Blocking Sema3A or its receptor Neuropilin1 (NRP1)

Patients CSF

Differential ultracentrifugation

miR-21

-Diagnosis/staging

⁴⁵

-Treatment tailoring

Patients CSF

Differential ultracentrifugation

mutant and wild-type IDH1 mRNA

-Diagnosis

⁴⁶

-Assessment of IDH1 mut status

In vitro (GBM stem cells)

-Size exclusion chromatography

-proteins related to ribosome, proteasome, cell adhesion, and extracellular matrix-receptor interaction.

-Diagnosis

⁴⁹

-Treatment tailoring/monitoring

-Differential ultracentrifugation

-EVs released by GSCs upon TMZ challenge display a specific enrichment in molecules involved in cell adhesion.

Patients’ plasma

Differential ultracentrifugation

members of the complement and coagulation cascade and regulators of iron metabolism (vWF, APCS, C4B, AMBP, APOD, AZGP1, C4BPB, Serpin3, FTL, C3, and APOE)

-Diagnosis

⁵¹

-Treatment tailoring/monitoring

In vitro (GBM stem cells, Cell lines), Mouse plasma

Differential ultracentrifugation

EGFR, PDGFRα, PDPN, EphA2, EGFRvIII, IDH1 R132H, HSP90, CD4124, MHCII.

-Diagnosis

⁵⁴

-Treatment tailoring/monitoring

-Predict response to therapy

Patients’ plasma

Patients’ serum

Differential ultracentrifugation

Survivin

-Diagnosis

⁵⁵

-Treatment tailoring/monitoring

-Predict response to therapy

Mouse plasma, Patients’ serum

Differential ultracentrifugation

IDH1G395A DNA

-Diagnosis

⁶⁴

-Assessment of IDH1 mut status

Patients’ serum

Differential ultracentrifugation

miRNA21, EGFRvIII mRNA Proteins: angiogenin, FGFα, IL-6, IL-8, TIMP-1, VEGF, and TIMP-2

-Diagnosis

⁶⁵

-Treatment tailoring/monitoring

In vitro (GBM Cell lines), Patients’ serum

Differential ultracentrifugation

EGFR protein and NLGN3, PTTG1 mRNA

-Diagnostic and prognostic markers

⁶⁶

Patients’ serum

PTEN RNA

-Diagnosis/staging

⁶⁷

Patients serum

Microfluidic platform

MGMT and APNG RNA

-Diagnosis

⁶⁸

-Treatment tailoring/monitoring

-Predict response to therapy

Mouse plasma

Differential ultracentrifugation

DNM3, p65, CD117, PTEN and p53 mRNA and protein

-Diagnosis

⁶⁹

In vitro (GBM Cell lines)

Density gradient ultracentrifugation

ANXA1, IGF2R, ITGB1, PDCD6IP, ACTR3, CALR, IPO5, MVP, PSMD2 proteins

-Diagnosis

⁸⁶

-Markers for more aggressive disease

In vitro (GBM stem cells, Cell lines)

Density gradient ultracentrifugation

EVs proteins content mirrors the phenotypic signature of the respective GBM cells

-Diagnosis

⁶³

-GBM subtyping

Patients serum

Total Exosome Isolation Kit

EGFRvIII RNA

-Diagnosis

⁷³

-Treatment tailoring/monitoring

-Anti-EGFRvIII treatment

-Vaccine

In vitro (GBM stem cells)

-Size exclusion chromatography

DNA methylome

-Diagnosis

⁷⁵

-GBM subtyping

-Differential ultracentrifugation

-Treatment tailoring/monitoring

Patients serum

Size exclusion chromatography

miR-182-5p, miR-328-3p, miR-339-5p, miR-340-5p, miR-485-3p, miR-486-5p, and miR-543

-Diagnosis

⁸²

Patients serum

Exoquick

1 small noncoding RNA (RNU6-1) and 2 microRNAs (miR-320 and miR-574-3p)

-Diagnosis

⁸³

Patients serum

Exoquick

miR-21, miR-222 and miR-124-3p

-Diagnosis

⁸⁵

-Treatment tailoring/monitoring

Source

Isolation method

Identified molecules

Potential clinical Applications

Ref.

Mouse plasma

Differential ultracentrifugation

EGFRvIII

-Diagnosis

²³

-Treatment tailoring/monitoring

-Anti-EGFRvIII treatment

-Vaccine

In vitro(cell lines; GBM stem cells)

Differential ultracentrifugation

CLIC1

-Treatment tailoring

²⁴

In vitro(cell lines), Mouse plasma, Patient’s plasma

Differential ultracentrifugation

Proteins: CAV1, IL8, PDGFs, MMPs, PTX3, CD26, PAI1,
Transcripts: ADM, LOX, IGFPB 3, BCL2, BNIP3, NDRG1, PLOD2, PAI1

-Diagnosis

²⁵

-Treatment tailoring/monitoring

-Assessment of GBM oxygenation status

-Angiogenesis inhibitors

In vitro (GBM stem cells)

Differential ultracentrifugation

miR-148a-3p, miR-9-5p, miR-16-2-3p, miR-182-5p, miR-9-3p, miR-22-3p, miR-186-5p, miR-378e

-Diagnosis

²⁶

-Treatment tailoring/monitoring

-Angiogenesis inhibitors

In vitro (GBM stem cells)

Differential ultracentrifugation

97 mRNAs (RP, OXPHOS, glycolysis)

-Diagnosis

²⁸

-Treatment tailoring/monitoring

In vitro (GBM cell line)

Differential ultracentrifugation

miR-21

-Diagnosis

²⁹

-Treatment tailoring/monitoring

In vitro (GBM stem cells)

Differential ultracentrifugation

miR-451, miR-21, miR-15b, miR-146a, miR-223

-Diagnosis

³⁰

-Treatment tailoring/monitoring

In vitro (GBM stem cells)

Differential ultracentrifugation

Proteins involved in leukocyte recruitment and focal adhesion mechanisms

-Treatment tailoring/monitoring

³¹

-Agents blocking CSF-1R

Patients’ serum

Differential ultracentrifugation

EGFR, EGFRvIII, and TGF-β

-Diagnosis

³³

-Treatment tailoring/monitoring

-Anti-EGFRvIII treatment

-Vaccine

In vitro(cell lines)

Differential ultracentrifugation

HSPs 90, 70, 60, and 27

-Diagnosis

³⁴

-Treatment tailoring/monitoring

-Vaccine

In vitro (GBM stem cells)

Differential ultracentrifugation

PD-L1 (protein and DNA)

-Diagnosis

³⁵

-Treatment tailoring/monitoring

Patients’ serum/plasma

-anti-PD1 receptor blocking antibody

-Tumor subtyping

Patients CSF

Differential ultracentrifugation

wtEGFR RNA, EGFRvIII RNA

-Diagnosis

³⁷

-Treatment tailoring/monitoring

-Anti-EGFRvIII treatment

-Vaccine

In vitro (GBM stem cells), Mouse serum, Patients’ serum

Differential ultracentrifugation

Sema3A

-Diagnosis

⁴⁰

-Treatment tailoring

-Blocking Sema3A or its receptor Neuropilin1 (NRP1)

Patients CSF

Differential ultracentrifugation

miR-21

-Diagnosis/staging

⁴⁵

-Treatment tailoring

Patients CSF

Differential ultracentrifugation

mutant and wild-type IDH1 mRNA

-Diagnosis

⁴⁶

-Assessment of IDH1 mut status

In vitro (GBM stem cells)

-Size exclusion chromatography

-proteins related to ribosome, proteasome, cell adhesion, and extracellular matrix-receptor interaction.

-Diagnosis

⁴⁹

-Treatment tailoring/monitoring

-Differential ultracentrifugation

-EVs released by GSCs upon TMZ challenge display a specific enrichment in molecules involved in cell adhesion.

Patients’ plasma

Differential ultracentrifugation

members of the complement and coagulation cascade and regulators of iron metabolism (vWF, APCS, C4B, AMBP, APOD, AZGP1, C4BPB, Serpin3, FTL, C3, and APOE)

-Diagnosis

⁵¹

-Treatment tailoring/monitoring

In vitro (GBM stem cells, Cell lines), Mouse plasma

Differential ultracentrifugation

EGFR, PDGFRα, PDPN, EphA2, EGFRvIII, IDH1 R132H, HSP90, CD4124, MHCII.

-Diagnosis

⁵⁴

-Treatment tailoring/monitoring

-Predict response to therapy

Patients’ plasma

Patients’ serum

Differential ultracentrifugation

Survivin

-Diagnosis

⁵⁵

-Treatment tailoring/monitoring

-Predict response to therapy

Mouse plasma, Patients’ serum

Differential ultracentrifugation

IDH1G395A DNA

-Diagnosis

⁶⁴

-Assessment of IDH1 mut status

Patients’ serum

Differential ultracentrifugation

miRNA21, EGFRvIII mRNA Proteins: angiogenin, FGFα, IL-6, IL-8, TIMP-1, VEGF, and TIMP-2

-Diagnosis

⁶⁵

-Treatment tailoring/monitoring

In vitro (GBM Cell lines), Patients’ serum

Differential ultracentrifugation

EGFR protein and NLGN3, PTTG1 mRNA

-Diagnostic and prognostic markers

⁶⁶

Patients’ serum

PTEN RNA

-Diagnosis/staging

⁶⁷

Patients serum

Microfluidic platform

MGMT and APNG RNA

-Diagnosis

⁶⁸

-Treatment tailoring/monitoring

-Predict response to therapy

Mouse plasma

Differential ultracentrifugation

DNM3, p65, CD117, PTEN and p53 mRNA and protein

-Diagnosis

⁶⁹

In vitro (GBM Cell lines)

Density gradient ultracentrifugation

ANXA1, IGF2R, ITGB1, PDCD6IP, ACTR3, CALR, IPO5, MVP, PSMD2 proteins

-Diagnosis

⁸⁶

-Markers for more aggressive disease

In vitro (GBM stem cells, Cell lines)

Density gradient ultracentrifugation

EVs proteins content mirrors the phenotypic signature of the respective GBM cells

-Diagnosis

⁶³

-GBM subtyping

Patients serum

Total Exosome Isolation Kit

EGFRvIII RNA

-Diagnosis

⁷³

-Treatment tailoring/monitoring

-Anti-EGFRvIII treatment

-Vaccine

In vitro (GBM stem cells)

-Size exclusion chromatography

DNA methylome

-Diagnosis

⁷⁵

-GBM subtyping

-Differential ultracentrifugation

-Treatment tailoring/monitoring

Patients serum

Size exclusion chromatography

miR-182-5p, miR-328-3p, miR-339-5p, miR-340-5p, miR-485-3p, miR-486-5p, and miR-543

-Diagnosis

⁸²

Patients serum

Exoquick

1 small noncoding RNA (RNU6-1) and 2 microRNAs (miR-320 and miR-574-3p)

-Diagnosis

⁸³

Patients serum

Exoquick

miR-21, miR-222 and miR-124-3p

-Diagnosis

⁸⁵

-Treatment tailoring/monitoring

Table 1

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Summary of the Reviewed EV-Associated Biomarkers with Potential Clinical Implications

Source	Isolation method	Identified molecules	Potential clinical Applications	Ref.
Mouse plasma	Differential ultracentrifugation	EGFRvIII	-Diagnosis	²³
			-Treatment tailoring/monitoring
			-Anti-EGFRvIII treatment
			-Vaccine
In vitro(cell lines; GBM stem cells)	Differential ultracentrifugation	CLIC1	-Treatment tailoring	²⁴
In vitro(cell lines), Mouse plasma, Patient’s plasma	Differential ultracentrifugation	Proteins: CAV1, IL8, PDGFs, MMPs, PTX3, CD26, PAI1, Transcripts: ADM, LOX, IGFPB 3, BCL2, BNIP3, NDRG1, PLOD2, PAI1	-Diagnosis	²⁵
			-Treatment tailoring/monitoring
			-Assessment of GBM oxygenation status
			-Angiogenesis inhibitors
In vitro (GBM stem cells)	Differential ultracentrifugation	miR-148a-3p, miR-9-5p, miR-16-2-3p, miR-182-5p, miR-9-3p, miR-22-3p, miR-186-5p, miR-378e	-Diagnosis	²⁶
			-Treatment tailoring/monitoring
			-Angiogenesis inhibitors
In vitro (GBM stem cells)	Differential ultracentrifugation	97 mRNAs (RP, OXPHOS, glycolysis)	-Diagnosis	²⁸
			-Treatment tailoring/monitoring
In vitro (GBM cell line)	Differential ultracentrifugation	miR-21	-Diagnosis	²⁹
			-Treatment tailoring/monitoring
In vitro (GBM stem cells)	Differential ultracentrifugation	miR-451, miR-21, miR-15b, miR-146a, miR-223	-Diagnosis	³⁰
			-Treatment tailoring/monitoring
In vitro (GBM stem cells)	Differential ultracentrifugation	Proteins involved in leukocyte recruitment and focal adhesion mechanisms	-Treatment tailoring/monitoring	³¹
			-Agents blocking CSF-1R
Patients’ serum	Differential ultracentrifugation	EGFR, EGFRvIII, and TGF-β	-Diagnosis	³³
			-Treatment tailoring/monitoring
			-Anti-EGFRvIII treatment
			-Vaccine
In vitro(cell lines)	Differential ultracentrifugation	HSPs 90, 70, 60, and 27	-Diagnosis	³⁴
			-Treatment tailoring/monitoring
			-Vaccine
In vitro (GBM stem cells)	Differential ultracentrifugation	PD-L1 (protein and DNA)	-Diagnosis	³⁵
			-Treatment tailoring/monitoring
Patients’ serum/plasma			-anti-PD1 receptor blocking antibody
			-Tumor subtyping
Patients CSF	Differential ultracentrifugation	wtEGFR RNA, EGFRvIII RNA	-Diagnosis	³⁷
			-Treatment tailoring/monitoring
			-Anti-EGFRvIII treatment
			-Vaccine
In vitro (GBM stem cells), Mouse serum, Patients’ serum	Differential ultracentrifugation	Sema3A	-Diagnosis	⁴⁰
			-Treatment tailoring
			-Blocking Sema3A or its receptor Neuropilin1 (NRP1)
Patients CSF	Differential ultracentrifugation	miR-21	-Diagnosis/staging	⁴⁵
			-Treatment tailoring
Patients CSF	Differential ultracentrifugation	mutant and wild-type IDH1 mRNA	-Diagnosis	⁴⁶
			-Assessment of IDH1 mut status
In vitro (GBM stem cells)	-Size exclusion chromatography	-proteins related to ribosome, proteasome, cell adhesion, and extracellular matrix-receptor interaction.	-Diagnosis	⁴⁹
			-Treatment tailoring/monitoring
	-Differential ultracentrifugation
		-EVs released by GSCs upon TMZ challenge display a specific enrichment in molecules involved in cell adhesion.
Patients’ plasma	Differential ultracentrifugation	members of the complement and coagulation cascade and regulators of iron metabolism (vWF, APCS, C4B, AMBP, APOD, AZGP1, C4BPB, Serpin3, FTL, C3, and APOE)	-Diagnosis	⁵¹
			-Treatment tailoring/monitoring
In vitro (GBM stem cells, Cell lines), Mouse plasma	Differential ultracentrifugation	EGFR, PDGFRα, PDPN, EphA2, EGFRvIII, IDH1 R132H, HSP90, CD4124, MHCII.	-Diagnosis	⁵⁴
			-Treatment tailoring/monitoring
			-Predict response to therapy
Patients’ plasma
Patients’ serum	Differential ultracentrifugation	Survivin	-Diagnosis	⁵⁵
			-Treatment tailoring/monitoring
			-Predict response to therapy
Mouse plasma, Patients’ serum	Differential ultracentrifugation	IDH1G395A DNA	-Diagnosis	⁶⁴
			-Assessment of IDH1 mut status
Patients’ serum	Differential ultracentrifugation	miRNA21, EGFRvIII mRNA Proteins: angiogenin, FGFα, IL-6, IL-8, TIMP-1, VEGF, and TIMP-2	-Diagnosis	⁶⁵
			-Treatment tailoring/monitoring
In vitro (GBM Cell lines), Patients’ serum	Differential ultracentrifugation	EGFR protein and NLGN3, PTTG1 mRNA	-Diagnostic and prognostic markers	⁶⁶
Patients’ serum	-	PTEN RNA	-Diagnosis/staging	⁶⁷
Patients serum	Microfluidic platform	MGMT and APNG RNA	-Diagnosis	⁶⁸
			-Treatment tailoring/monitoring
			-Predict response to therapy
Mouse plasma	Differential ultracentrifugation	DNM3, p65, CD117, PTEN and p53 mRNA and protein	-Diagnosis	⁶⁹
In vitro (GBM Cell lines)	Density gradient ultracentrifugation	ANXA1, IGF2R, ITGB1, PDCD6IP, ACTR3, CALR, IPO5, MVP, PSMD2 proteins	-Diagnosis	⁸⁶
			-Markers for more aggressive disease
In vitro (GBM stem cells, Cell lines)	Density gradient ultracentrifugation	EVs proteins content mirrors the phenotypic signature of the respective GBM cells	-Diagnosis	⁶³
			-GBM subtyping
Patients serum	Total Exosome Isolation Kit	EGFRvIII RNA	-Diagnosis	⁷³
			-Treatment tailoring/monitoring
			-Anti-EGFRvIII treatment
			-Vaccine
In vitro (GBM stem cells)	-Size exclusion chromatography	DNA methylome	-Diagnosis	⁷⁵
			-GBM subtyping
	-Differential ultracentrifugation		-Treatment tailoring/monitoring
Patients serum	Size exclusion chromatography	miR-182-5p, miR-328-3p, miR-339-5p, miR-340-5p, miR-485-3p, miR-486-5p, and miR-543	-Diagnosis	⁸²
Patients serum	Exoquick	1 small noncoding RNA (RNU6-1) and 2 microRNAs (miR-320 and miR-574-3p)	-Diagnosis	⁸³
Patients serum	Exoquick	miR-21, miR-222 and miR-124-3p	-Diagnosis	⁸⁵
			-Treatment tailoring/monitoring

Source	Isolation method	Identified molecules	Potential clinical Applications	Ref.
Mouse plasma	Differential ultracentrifugation	EGFRvIII	-Diagnosis	²³
			-Treatment tailoring/monitoring
			-Anti-EGFRvIII treatment
			-Vaccine
In vitro(cell lines; GBM stem cells)	Differential ultracentrifugation	CLIC1	-Treatment tailoring	²⁴
In vitro(cell lines), Mouse plasma, Patient’s plasma	Differential ultracentrifugation	Proteins: CAV1, IL8, PDGFs, MMPs, PTX3, CD26, PAI1, Transcripts: ADM, LOX, IGFPB 3, BCL2, BNIP3, NDRG1, PLOD2, PAI1	-Diagnosis	²⁵
			-Treatment tailoring/monitoring
			-Assessment of GBM oxygenation status
			-Angiogenesis inhibitors
In vitro (GBM stem cells)	Differential ultracentrifugation	miR-148a-3p, miR-9-5p, miR-16-2-3p, miR-182-5p, miR-9-3p, miR-22-3p, miR-186-5p, miR-378e	-Diagnosis	²⁶
			-Treatment tailoring/monitoring
			-Angiogenesis inhibitors
In vitro (GBM stem cells)	Differential ultracentrifugation	97 mRNAs (RP, OXPHOS, glycolysis)	-Diagnosis	²⁸
			-Treatment tailoring/monitoring
In vitro (GBM cell line)	Differential ultracentrifugation	miR-21	-Diagnosis	²⁹
			-Treatment tailoring/monitoring
In vitro (GBM stem cells)	Differential ultracentrifugation	miR-451, miR-21, miR-15b, miR-146a, miR-223	-Diagnosis	³⁰
			-Treatment tailoring/monitoring
In vitro (GBM stem cells)	Differential ultracentrifugation	Proteins involved in leukocyte recruitment and focal adhesion mechanisms	-Treatment tailoring/monitoring	³¹
			-Agents blocking CSF-1R
Patients’ serum	Differential ultracentrifugation	EGFR, EGFRvIII, and TGF-β	-Diagnosis	³³
			-Treatment tailoring/monitoring
			-Anti-EGFRvIII treatment
			-Vaccine
In vitro(cell lines)	Differential ultracentrifugation	HSPs 90, 70, 60, and 27	-Diagnosis	³⁴
			-Treatment tailoring/monitoring
			-Vaccine
In vitro (GBM stem cells)	Differential ultracentrifugation	PD-L1 (protein and DNA)	-Diagnosis	³⁵
			-Treatment tailoring/monitoring
Patients’ serum/plasma			-anti-PD1 receptor blocking antibody
			-Tumor subtyping
Patients CSF	Differential ultracentrifugation	wtEGFR RNA, EGFRvIII RNA	-Diagnosis	³⁷
			-Treatment tailoring/monitoring
			-Anti-EGFRvIII treatment
			-Vaccine
In vitro (GBM stem cells), Mouse serum, Patients’ serum	Differential ultracentrifugation	Sema3A	-Diagnosis	⁴⁰
			-Treatment tailoring
			-Blocking Sema3A or its receptor Neuropilin1 (NRP1)
Patients CSF	Differential ultracentrifugation	miR-21	-Diagnosis/staging	⁴⁵
			-Treatment tailoring
Patients CSF	Differential ultracentrifugation	mutant and wild-type IDH1 mRNA	-Diagnosis	⁴⁶
			-Assessment of IDH1 mut status
In vitro (GBM stem cells)	-Size exclusion chromatography	-proteins related to ribosome, proteasome, cell adhesion, and extracellular matrix-receptor interaction.	-Diagnosis	⁴⁹
			-Treatment tailoring/monitoring
	-Differential ultracentrifugation
		-EVs released by GSCs upon TMZ challenge display a specific enrichment in molecules involved in cell adhesion.
Patients’ plasma	Differential ultracentrifugation	members of the complement and coagulation cascade and regulators of iron metabolism (vWF, APCS, C4B, AMBP, APOD, AZGP1, C4BPB, Serpin3, FTL, C3, and APOE)	-Diagnosis	⁵¹
			-Treatment tailoring/monitoring
In vitro (GBM stem cells, Cell lines), Mouse plasma	Differential ultracentrifugation	EGFR, PDGFRα, PDPN, EphA2, EGFRvIII, IDH1 R132H, HSP90, CD4124, MHCII.	-Diagnosis	⁵⁴
			-Treatment tailoring/monitoring
			-Predict response to therapy
Patients’ plasma
Patients’ serum	Differential ultracentrifugation	Survivin	-Diagnosis	⁵⁵
			-Treatment tailoring/monitoring
			-Predict response to therapy
Mouse plasma, Patients’ serum	Differential ultracentrifugation	IDH1G395A DNA	-Diagnosis	⁶⁴
			-Assessment of IDH1 mut status
Patients’ serum	Differential ultracentrifugation	miRNA21, EGFRvIII mRNA Proteins: angiogenin, FGFα, IL-6, IL-8, TIMP-1, VEGF, and TIMP-2	-Diagnosis	⁶⁵
			-Treatment tailoring/monitoring
In vitro (GBM Cell lines), Patients’ serum	Differential ultracentrifugation	EGFR protein and NLGN3, PTTG1 mRNA	-Diagnostic and prognostic markers	⁶⁶
Patients’ serum	-	PTEN RNA	-Diagnosis/staging	⁶⁷
Patients serum	Microfluidic platform	MGMT and APNG RNA	-Diagnosis	⁶⁸
			-Treatment tailoring/monitoring
			-Predict response to therapy
Mouse plasma	Differential ultracentrifugation	DNM3, p65, CD117, PTEN and p53 mRNA and protein	-Diagnosis	⁶⁹
In vitro (GBM Cell lines)	Density gradient ultracentrifugation	ANXA1, IGF2R, ITGB1, PDCD6IP, ACTR3, CALR, IPO5, MVP, PSMD2 proteins	-Diagnosis	⁸⁶
			-Markers for more aggressive disease
In vitro (GBM stem cells, Cell lines)	Density gradient ultracentrifugation	EVs proteins content mirrors the phenotypic signature of the respective GBM cells	-Diagnosis	⁶³
			-GBM subtyping
Patients serum	Total Exosome Isolation Kit	EGFRvIII RNA	-Diagnosis	⁷³
			-Treatment tailoring/monitoring
			-Anti-EGFRvIII treatment
			-Vaccine
In vitro (GBM stem cells)	-Size exclusion chromatography	DNA methylome	-Diagnosis	⁷⁵
			-GBM subtyping
	-Differential ultracentrifugation		-Treatment tailoring/monitoring
Patients serum	Size exclusion chromatography	miR-182-5p, miR-328-3p, miR-339-5p, miR-340-5p, miR-485-3p, miR-486-5p, and miR-543	-Diagnosis	⁸²
Patients serum	Exoquick	1 small noncoding RNA (RNU6-1) and 2 microRNAs (miR-320 and miR-574-3p)	-Diagnosis	⁸³
Patients serum	Exoquick	miR-21, miR-222 and miR-124-3p	-Diagnosis	⁸⁵
			-Treatment tailoring/monitoring

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