Table 1

Summary of current glioma biomarker candidates and their associations with diagnosis, treatment and prognosis

BiomarkerAssociations
DiagnosisTreatmentPrognosis
Circulating tumour cells↑ with disease progression (Sullivan et al 2014).26
↑ in IDH wildtype high-grade gliomas (Li et al, 2019).27
↓ postradiotherapy (MacArthur et al, 2014).30
Extracellular vesicles↑ in glioblastoma (Osti et al, 2019).34
Exosomal protein levels correlated with WHO glioma grade (Muller et al, 2015).25
EGFR-positive serum EVs correlated with glioma malignancy (Wang et al, 2019).42
↓ with temozolomide in T103 mice (Shao et al, 2012).32
TPI from T103 mouse microvesicle measurements revealed response to temozolomide before observable changes in tumour size (Shao et al, 2012).32
TPI from microvesicle measurements predicted response to temozolomide and radiotherapy (Shao et al, 2012).32
↑ release after radiation (Arscott et al, 2013).38
↑ release of EV adhesion molecules after temozolomide treatment (Andre-Gregoire et al, 2018).39
Circulating tumour DNActDNA sequencing facilitated diagnosis of diffuse gliomas (Martínez-Ricarte et al, 2018).47ctDNA in CSF of patients with glioma contributed to fourfold increased risk of mortality (Miller et al, 2019).46
MicroRNAs↑ exosomal miR-21, miR-222 and miR-124–3p in patients with high-grade glioma (Santangelo et al, 2018).53
↑ miR-21 in human glioblastoma cell lines, serum and tissue (Yang et al, 201455; Skog et al, 2008; Chan et al, 2005).56
↑ miR-21 in high-grade gliomas (Chan et al, 2005).56
Serum miR-181 level correlated with response to temozolomide in patients with glioblastoma (Zhang et al, 2012).54
↓ miR-21, miR-222 and miR-124–3p levels in postsurgery blood samples of patients with glioma (Santangelo et al, 2018).53
miR-21 downregulation boosted the proapoptotic effect of temozolomide in glioblastoma cells (Lan et al, 2015).58
miR-21 overexpression in U87MG cells inhibited temozolomide-mediated apoptosis (Shi et al, 2010).59
Patients with glioblastoma with lower risk scores from miRNA expression profiles had longer survival (Li et al, 2014).52
miR-21 levels inversely correlated with patient survival (Yang et al, 2014).55
Epidermal growth factor receptor variant III↑ microvesicle EGFRvIII in glioblastoma cells (Shao et al, 2012).32↓ microvesicle EGFRvIII with temozolomide and geldanamycin (Shao et al, 2012).32
YKL-40↑ in glioblastoma (Shostak et al 200364 ; Qin et al, 2017).65
↓ in patients with radiographically absent disease (Hormigo et al, 200666 ; Iwamoto et al, 2011).67
↑ in patients who had undergone partial resection, compared with total resection (Bernardi et al, 2012).68↑ YKL-40 associated with worse survival (Qin et al, 2017).65
Matrix metalloproteinase-9↑ in patients with glioblastoma with radiographically evident disease (Hormigo et al, 2006).66↑ MMP-9 in the CSF of patients with recurrent glioma treated with doxycycline suggested a failed response to treatment (Wong et al, 2008).73
↑ serum MMP-9 in high-grade glioma after surgical resection (Hormigo et al, 2006).66
HaptoglobinExpression levels proportional to increasing tumour grade (Kumar et al, 2010).75Haptoglobin overexpression in tumours implanted in mice resulted in a worse prognosis (Kumar et al, 2010).75
A2-Heremans-Schmid glycoprotein↓ AHSG expression linked to lower median survival time (Petrik et al, 2008).76
S100A8/A9↑ in glioblastoma sera (Arora et al, 2019).78↑ transcript levels linked to lower median survival time (Arora et al, 2019).78
  • AHSG, A2-Heremans-Schmid glycoprotein; CSF, cerebrospinal fluid; ctDNA, circulating tumour DNA; EGFR, epidermal growth factor receptor; EGFRvIII, EGFR variant III; EVs, extracellular vesicles; IDH, isocitrate dehydrogenase; miRNA, microRNA; MMP-9, matrix metalloproteinase-9; TPI, tumour progression index.