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Table 1 MiRNAs from blood derived products (Serum/Plasma/Blood cells) as brain tumor biomarkers

From: MicroRNA based theranostics for brain cancer: basic principles

miRNA ↑/↓ Study, Year, Ref. Biological fluid and Analysis method No. of pts. Significance Area under the Curve (AUC) Sensitivity (SS) Specificity (SP)
miR-21 Wang, 2012 [100] Plasma 30 Glioma Distinguishes between GBM and healthy controls Glioma vs. healthy controls
qRT-PCR (10 Gr II) Expression levels cannot distinguish between glioma grades AUC = 0.9300 (95% CI: 0.7940–1.066)
  (10 Gr III) Cannot distinguish between glioma and other brain tumors SS = 90.0%
(10 Gr IV)   SP = 100%
10 Meningioma   
10 Hyphophysoma
10 Healthy controls
miR-29 Wu, 2015 [106] Serum 83 Glioma Distinguishes HGGa from healthy controls AUC = 0.81 (95% CI, 0.73–0.89).
qRT-PCR (36 Gr I-II) Not a brain cancer specific marker  
  (47 Gr III-IV)  
69 Healthy controls
miR-21 D’Urso, 2015 [101] Blood 30 Glioma Combined diagnostic tree using miR-15b and miR-21 can distinguish glioma from other conditions Combined miR-15b and mir21
miR-15b   Microarray (8 Gr II) SS = 90%
miR-16   qRT-PCR (6 Gr III) Mir-16 levels could distinguish between grades of Glioma (lowest expression in GBM) SP = 100%
(16 Gr IV) miR-16 to distinguish between Gr IV and II/III
30 Various neurological AUC = 0.98
disorders SS = 0.98%
36 PCNSLc SP = 99%
16 Secondary brain
metastases
miR-21 Santangelo, 2018 Serum 100 Glioma Higher serum levels of 3 miRNA panel in GBM and HGG compared to LGGb and healthy controls Cumulative 3 miRNA panel; GBM vs healthy:
miR-222 [102] Exosomes (2 Gr I) Cumulative 3 miRNA panel distinguishes between GBM, HGG, LGG and healthy controls AUC = 0.87 (95% CI 0.7885–0.9524, p < 0.0001)
miR-124-3p qRT-PCR (13 Gr II) High serum levels return to normal postoperatively SS = 84%
(16 Gr III) SP = 77%
(69 Gr IV) *For HGG, LGG, Metastases vs healthy control, see original article
11 Brain metastases
30 Healthy controls
miR-203 Chen, 2017 [107] Serum 70 GBMd Distinguishes between GBM and LGG, GBM and healthy controls GBM vs LGG
   qRT-PCR 30 LGG Lower serum level correlated with larger tumor size, lower KPSe score, lower OSf and lower PFSg AUC = 0.814
  30 Healthy controls GBM vs healthy controls
AUC = 0.862
miR-137 Li, 2016 [108] Serum 64 glioma Downregulated levels in glioma compared to controls NA
qRT-PCR (35 Gr I/II) Further downregulation in HGG
  (29 Gr III/IV) 64 Controls Low levels associated with lower OS of glioma patients
miR-185 Tang, 2015 [103] Serum 66 Glioma Downregulation of mir-185 specifically associated with glioma patients compared to oncologic non-glioma patients NA
qRT-PCR (23-Gr I + II) Lower serum mir-185 levels in Grade III-IV glioma compared to Grade I-II
(43-Gr III + IV) Lower mir-185 levels correlated with lower OS
11 Pituitary adenoma Up-regulation of mir-185 levels after chemoradiation
32 Meningioma
14 Acoustic neuroma
miR-210 Lai, 2015 [109] Serum 136 Glioma Upregulation of mir-210 can distinguish glioma from healthy controls Overall glioma (Gr I-IV) vs healthy controls
qRT-PCR (13 Gr I) miR-210 levels associated with tumor grade AUC value of 0.927 (95% CI1/40.889–0.964)
(35 Gr II) (Upregulation trend in glioma Gr I-II vs healthy controls; Statistical significant upregulation in Gr III-IV vs healthy controls) NPV = 72.5%
(46 Gr III) High mir-210 levels associated with lower OS PPV = 91.3%
(32 Gr IV) SS = 91.27%
50 Healthy controls SP = 72.50%
miR-205 Yue, 2016 [104] Serum 64 Glioma Significant downregulation of mir-205 in all grades glioma compared to healthy controls Overall glioma (Gr I-IV) vs healthy controls
qRT-PCR (7 Gr I) Stepwise decrease in serum mir-205 levels with ascending pathological grades AUC = 0.935
(9 Gr II) Significantly lower mir-205 levels in glioma versus other brain-tumors PPV = 96.4%,
(21 Gr III) Downregulation of mir-205 correlated with KPS score and OS NPV = 65.8%,
(27 Gr IV) SS = 86.3%,
45 Healthy controls SP = 92.2%,
8 Meningioma
6 PCNSL
5 Pituitary adenoma
miR-221/222 Family Zhang, 2016 [110] Serum 50 Glioma Distinguishes glioma from healthy controls miR-221:
qRT-PCR 51 Healthy controls AUC = 0.84 (95% CI: 0.74–0.93)
miR-222:
AUC = 0.92 (95% CI 0.87–0.94)
miR-301a Lan, 2018 [105] Serum exosomes 60 Glioma Higher levels in glioma vs controls NA
qRT-PCR 43 Heallthy controls Higher levels in glioma vs other types of cancers
9 Meningioma Higher levels correlated with ascending pathological grades and lower KPS
7 PCNSL Levels decrease postoperatively
10 Pituitary adenoma Secondary increase may reflect local recurrence
Serum levels in HGG are independently associated with longer OS
miR-397a Huang, 2017 [113] Serum 100 Glioma Distinguishes glioma from healthy controls miR-376a: AUC = 0.872; SS = 81.0%; SP = 82.0%
miR-397b
miR-397c
qRT-PCR (10 Gr I) Decreased levels associated with advanced WHO grade and low KPS miR-376b: AUC = 0.890; SS = 82.0% SP = 78.0%;
(20 Gr II) Higher miRNA levels associated with better OS miR-376c: AUC = 0.837; SS = 90.0%; SP = 70.0%
(30 Gr III)
(40 Gr IV)
150 Healthy controls
miR-122 Tang, 2017 [114] Plasma 74 Glioma Distinguishes between glioma and healthy controls AUC = 0.939
qRT-PCR (14 Gr I) Further downregulation of serum levels in higher grade gliomas SS = 91.9%
(17 Gr II) The miRNA level is an independent prognostic factor for OS SP = 81.1%
(20 Gr III)
(23 Gr IV)
74 Healthy controls
miR-125b Regazzo, 2016 [112] Serum 22 Glioma Distinguishes between GBM and lower grade (II/III) gliomas miR-125b: GBM vs lower grade glioma, AUC = 0.75 (95%
miR-497
qRT-PCR (12 Gr II/III)   CI = 0.533–0.967)
(10 Gr IV) miR-497: GBM vs lower grade glioma, AUC = 0.87 (95%
8 Meningioma confidence interval (CI) = 0.712–1
15 Healthy controls
miR-125b Wei, 2016 [111] Serum 33 Glioma Distinguishes between glioma and healthy controls Glioma vs healthy controls
qRT-PCR (11 Gr I)   AUC = 0.839 (95% CI: 0.743–0.935)
(11 Gr II)
(11 Gr III/IV)
33 Healthy controls
miR-182 Xiao, 2016 [115] Serum 112 Glioma Distinguishes between glioma and healthy controls Glioma vs healthy controls
qRT-PCR (18 Gr I) The expression levels associated with KPS score and WHO grade and correlated with lower OS and DFS, AUC = 0.778
(23 Gr II) The level is independent prognostic factor for OS SS = 58.5%
(32 Gr II)   SP = 85.2%
(39 Gr IV)
54 Healthy controls
miR-128 Sun, 2015 [121] Serum 151 Glioma Distinguishes between glioma and healthy controls and meningioma Glioma vs healthy controls
qRT-PCR (24 Gr I) Distinguishes Gr II-IV from Gr I AUC = 0.9095
(23 Gr II) Levels elevated after surgery and correlate with the pathological grade and KPS Glioma vs Meningioma
(43 Gr III) AUC = 0.8283
(61 Gr IV) Glioma II-IV vs I
59 Post-op glioma AUC = 0.7362
52 Meningioma
53 Healthy controls
30 Glioma
miR-128 Wang, 2012 [100] Plasma (10 Gr II) Can distinguish between GBM and healthy controls AUC (miR-128 or miR-342-3p) = 1.000 (95% CI: 1.000–1.000)
miR-342-3p   qRT-PCR (10 Gr III) Decreased levels correlated with glioma grade SS = 90.0%
(10 Gr IV) Significant upregulation after operation and chemoradiation SP = 100%
10 meningioma
10 Hyphophysoma
10 Healthy controls
miR-128 Roth, 2011 [120] Blood cells 20 Glioblastoma Distinguishes between GBM and healthy controls GBM vs healthy controls
miR-342-3p   Microarray 20 Healthy Controls Authors apply statistic learning techniques (SVM = Support vector machines) and compute the diagnostic accuracy of miRNA profiles; a 180 miRNA signature calculated to have the highest diagnostic accuracy in distinguishing GBM from healthy controls. miR-128:
qRT-PCR    AUC = 0.828
miR-342-3p
AUC = 0.18
180 miRNA signature:
SS = 83%
SP = 79%
RNU6–1 Manterola, 2014 Serum exosomes Initial screening 3 small non coding RNAs can distinguish between GBM and healthy controls RNU6–1
miR-320 [119] Low density array 25 Glioblastoma (machine learning algorithm) AUC = 0.852 (95% CI, 0.74–0.96)
miR-574-3p   qRT-PCR 25 Healthy controls   SS = 73%; SP = 70%
Confirmation Results from initial screening not confirmed is the second study group, only RNU6–1 was found significantly up-regulated! miR-320
50 Glioblastoma AUC = 0.720
30 Healthy controls (95% CI, 0.56–0.87)
SS = 65%; SP = 65%
miR-574-3p
AUC = 0.738 (95% CI, 0.58–0.89)
SS = 59%; SP = 59%
3 sncRNA signature:
AUC = 0.926 (95%[CI], 0.84–1)
SS = 87%; SP = 86%
miR-454-3p Shao, 2015 [117] Plasma 70 Glioma Distinguishes between glioma and healthy controls Glioma vs healthy controls
qRT-PCR (8 Gr I) Higher levels in higher WHO grades and the levels decrease significantly postoperatively AUC = 0.9063 [95% (CI): 0.8487–0.9639)]
(15 Gr II) Weak correlation between high levels and OS SS = 99.05%
(25 Gr III) SP = 82.86%
(22 Gr IV)
70 Healthy controls
miR-451a Zhao, 2016 [116] Serum 118 Glioma Distinguishes between glioma and healthy controls Glioma vs healthy controls
qRT-PCR (27 Gr I) Levels return to almost healthy control expression 7 days after surgery AUC = 0.816
(33 Gr II) The expression level downregulation correlates with WHO grade and KPS SS = 81.4%
(33 Gr III) SP = 79.7%
(25 Gr IV)
84 Healthy controls
miR-15b-5p Yang, 2013 [122] Serum 148 Glioma Significantly decreased in glioma (Gr I-IV) compared to healthy controls SS = 88.00%
miR-23a
miR-133a
miR-150*
miR-197 Solexa sequencing (15 Gr I) Malignant astrocytoma prediction SP = 97.87%
miR- 497
miR-548b-5p qRT-PCR (55 Gr II) Significant postoperative upregulation of aforementioned miRNAs
(45 Gr III)
(33 Gr IV)
11 Astrogliosis
80 Healthy controls
miR-15b-5p Zhi, 2015 [123] Serum 90 Glioma Combined 9 miRNA panel distinguishes glioma from healthy controls AUC = 0.9722 (95% CI, 0.9501–0.9942)
miR-16-5p
miR-19a-3p
miR-19b-3p
miR-20a-5p TaqMan (28 Gr II) Levels decrease postoperatively SS = 93.3%
miR-106a-5p
miR-130a-3p Low density Array (38 Gr III) miR-20a-5p, miR-106a-5p, and miR-181b-5p associated with advanced glioma stages SP = 94.5%
miR-181b-5p
miR-208a-3p
qRT-PCR (24 Gr IV) miR-19a-3p, miR-106a-5p, and miR-181b-5p significantly associated lower OS.
110 Healthy controls
miR-17 Xu, 2017 [118] Serum 47 Glioma Distinguishes between glioma and healthy controls miR-17; AUC = 0.787 [95% (CI): 0.690–0.865)] SS = 89.3%; SP = 55.3% miR-130a AUC = 0.720 [95% (CI): 0.617–0.807)] SS = 70%; SP = 65.2% miR-10b AUC = 0.721 [95% (CI): 0.619–0.808)] SS = 44.6%; SP = 93.6% miR-Score (all three miRNA) AUC = 0.872 [95% (CI): 0.787–0.932)] SS = 72.3%; SP = 85.1%
miR-130a   qRT-PCR (16 Gr I-II) Higher serum levels in HGG compared to LGG
miR-10b (31 Gr III-IV)
45 Healthy controls
miR-93 Goze, 2018 [124] Whole blood 15 DLGGh 3 miRNA signature tree distinguishes DLGG from healthy controls miRNA-93; AUC = 0.83556
miR-590-3p
miR-454 TaqMan OpenArray RT-qPCR platform 15 Healthy controls miRNA-590-3p; AUC = 0.8133
miRNA-454; AUC = 0.75111
  1. 1HGG High grade glioma, 2LGG Low-grade glioma, 3PCNSL Primary central nervous system lymphoma, 4GBM Glioblastoma, 5KPS Karnofsky Performance Scale, 6OS Overall Survival, 7PFS Progression free survival, 8DLGGdiffuse large grade glioma