Table 1.
Main characteristics of the studies included in the meta-analysis
| Authors, publication year | Country, Duration (year) | Exosomal miR(s) | Cancer type | Detection method | Exosome extraction method | sample | Sample size (cancer) | mean/ median age (year) | Gender cancer (M/F) | TNM Stage | Outcome | Hazard ratio (HR) | Follow up (month) | Spec % | Sen % | AUC (95% CI) | NOS |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Up-regulationa | |||||||||||||||||
| Soeda N 2019 [35] | Japan 2006–2015 | miR-21 | GC | qRT-PCR | UC | plasma | 129 | 68 | 90/39 | II—III | OS, RFS |
OS: R-Multi/ R-Uni RFS: R-Multi/ R-Uni |
40.8 | 76.8 | 61.6 | NA | good |
| Sun L 2020 [36] | China NA | miR-122 | CRC | qRT-PCR | UC | serum | 85 | 65 | 46/39 | I—IV | OS | R-Multi/ R-Uni | 60 | NA | NA | NA | poor |
| Liu X 2018 [37] | China NA | miR-27a, miR-130a | CRC | qRT-PCR | Exosome isolation kit | plasma | 130 | 64 | 80/50 | I—IV | OS | R-Uni | 60 |
90.9 100 |
81.8 69.3 |
0.866 (0.774–0.957) 0.816 (0.730–0.901) |
poor |
| Wu L. 2020 [38] | China 2018–2019 |
miR-21 miR-210 |
PC | RT-qPCR | Exosome isolation kit | serum | 30 | 60 |
20/10 23/7 |
I—IV | NA | NA | NA |
90.0 90.0 |
80.0 83.0 |
0.869 0.823 |
good |
| Takahasi K 2018 [39] | Japan 2013- 2017 | miR-451a | PDAC | qRT-PCR | UC | plasma | 50 |
High expression group: 66 Low expression group: 69 |
28/22 | I—II | OS, DFS |
OS: R-Multi/ R-Uni DFS: R-Multi/ R-Uni |
30 (range: 5.5–54) |
70.8 | 69.2 | NA | good |
| Tsukamoto M 2017 [40] | Japan 2002- 2012 | miR-21 | CRC | RT-qPCR | UC | plasma | 326 | NA | NA | I—IV | OS, DFS |
OS: R-Multi DFS: R-Multi |
55 | NA | NA | NA | poor |
| Yokota Y 2021 [41] | Japan 2012–2015 | miR-638 | HCC | RT-qPCR | Exosome isolation kit | serum | 54 |
High expression group: 73 Low expression group: 70 |
35/19 | NA | DFS | R-Multi/ R-Uni | 24 | NA | NA | NA | good |
| Takano Y 2017 [42] | Japan 2005- 2012 | miR-203 | CRC | RT-qPCR | UC | serum | 240 | NA | 147/93 | I—IV | OS, DFS |
OS: R-Multi/ R-Uni DFS: R-Multi/ R-Uni |
54 | NA | NA | NA | poor |
| Tian X 2019 [43] | China 2009–2012 |
miR-21 miR-10b |
HCC | qRT-PCR | ExoQuick kit | serum | 124 | 48 | 115/9 | NA | DFS | R-Multi/ R-Uni | NA | NA | NA | NA | poor |
| Wei S.C. 2020 [44] | China NA | miR-15b-3p | GC | qRT-PCR | UC | serum | 108 | 62 | 80/28 | I—IV | OS | E | NA | 80.6 | 74.1 | 0.820 (0.763–0.876) | good |
| Xue X. F. 2019 [45] | China 2015–2017 |
miR-122 miR‐125b miR‐145 miR‐192 miR‐194 miR‐29a miR‐17‐5p miR‐106a |
HCC | qRT-PCR | Exosome isolation kit | serum | 80 | 59 | 61/19 | I—IV | OS | E | 24 | NA | NA |
0.746 (0.650–0.842) 0.650 (0.526–0.774) 0.535 (0.422–0.649) 0.752 (0.658–0.846) 0.738 (0.638–0.838) 0.703 (0.597–0.809) 0.850 (0.764–0.936) 0.704 (0.534–0.873) |
good |
| Yagi T 2019 [46] | Japan NA | miR-125b | CRC | qRT-PCR | UC | plasma | 6 | 65 | 4,2 | III—IV | PFS | R-Multi/ R-Uni | 12 | NA | NA | NA | good |
| Yan S. S. 2018 [47] | China NA | miR-6803-5p | CRC | qRT-PCR | Exosome isolation kit | serum | 168 | 55 | 100/68 | I—IV | OS, DFS |
OS: R-Multi DFS: R-Multi |
60 | NA | NA | 0.739 | poor |
| Matsumura T. 2015 [48] | Japan 1992–2007 | miR-19a | CRC | qRT-PCR | UC | serum | 209 | 65 | 80/129 | I—IV | OS, DFS |
OS: R-Multi/ R-Uni DFS: R-Multi/ R-Uni |
55.68 | NA | NA | NA | poor |
| Kawamura S. 2019 [49] | Japan 2013- 2018 |
miR-4525 miR-451a miR-21 |
PDAC | qRT-PCR | UC | plasma | 55 |
miR-4525: 66 miR-451a: 69 miR-21: 70 |
33/22 | I—II | OS, DFS |
OS: R-Multi/ R-Uni DFS: R-Multi/ R-Uni |
60 |
86.4 77.3 72.7 |
81.8 72.7 72.7 |
NA | poor |
| Abd El Gwad A. 2018 [50] | Egypt 2015–2016 | miR-1262 | HCC | qRT-PCR | UC | serum | 60 | 58 | 43/17 | N/A | RFS | E | 44 | 80.0 | 95.0 | 0.847 | good |
| Cui Y. 2019 [51] | China 2014–2016 | miR-224 | HCC | qRT-PCR | Exosome isolation kit | serum | 89 | 59 | 43/46 | N/A | OS | E | NA | NA | NA | 0.910 (0.840–0.980) | fair |
| Feng C. 2019 [52] | China NA | miR-196a-1 | GC | qRT-PCR | Exosome isolation kit | plasma | 86 | NA | NA | I—IV | OS | E | NA | NA | NA | NA | poor |
| Liu W. B. 2016 [53] | China 2008–2013 | miR-21 | HB | qRT-PCR | ExoQuick kit | serum | 32 | NA | 17/15 | I—IV | DFS | R-Multi/ R-Uni | 42 | NA | NA | 0.861 (0.752–0.935) | poor |
| Cho H. J. 2020 [54] | Korea 2014–2018 |
miR-25-3p miR-1269a miR-4661-5p miR-4746-5p |
HCC |
Cohoort1: NGS-RNA-Seq Cohort 2&3: qRT-PCR |
ExoQuick kit | serum | 72 | 55 | 58/14 | I—IV | NA | NA | NA | 71.4 | 38.0 | 0.704 (0.629–0.772) | good |
| Han J. Y. 2020 [55] | China 2015–2017 |
hsa-miR-100-5p hsa-miR-92a-3p hsa-miR-30e-5p hsa-miR-144-5p hsa-let-7i-5p has-miR-16 |
CRC | qRT-PCR | Exosome isolation kit | plasma | 139 | 60 | 77/62 | III—IV | OS | R-Uni | NA | NA | NA |
0.637 (0.545 -0.729) 0.659 (0.568–0.751) 0.694 (0.606–0.782) 0.791 (0.718 -0.864) 0.650 (0.559–0.742) 0.721 (0.638–0.804) 0.746 (0.664–0.827) 0.778 (0.702–0.854) |
good |
| de Miguel-Pérez D 2020 [56] | Spain NA |
miR-92a miR-222 |
CRC | qRT-PCR | UC | serum | 44 | 55 | 30/14 | NA | OS, DFS/PFS |
miR-92a OS: R-Uni DFS/PFS: R-Multi/ R-Uni miR-222 OS: R-Multi/ R-Uni |
27 | NA | NA |
0.951 (0.900–1.000) 0.896 (0.810–0.980) |
good |
| Qu Z. 2017 [57] | China NA | miR-665 | HCC | qRT-PCR | ExoQuick kit | serum | 30 | 60 | 12/18 | I—IV | OS | E | NA | NA | NA | NA | poor |
| Reese M. 2020 [58] | Germany 2015–2018 |
miR-200b miR-200c |
PDAC | qRT-PCR | UC | serum | 56 | 60 | 36/20 | I—IV | OS |
miR-200b OS: R-Multi/ R-Uni miR-200c OS: R-Multi/ R-Uni |
13 | NA | NA |
0.790 (0.680–0.890) 0.670 (0.550–0.790) |
good |
| Meltzer S. 2019 [59] | Norway NA |
miR-141-3p miR-375 |
LARC | qRT-PCR | Exosome isolation kit | plasma | 64 | 60 | 36/28 | NA | OS, PFS |
OS: R-Uni PFS: R-Uni |
65 (range 4–66) | NA | NA | NA | good |
| Wang Q. 2021 [60] | China NA | miR-1290 | HCC | qRT-PCR | Exosome isolation kit/UC | serum | 49 | 55 | 37/12 | I—IV | NA | NA | NA | NA | NA | NA | poor |
| Zhang Y. 2021 [60] | China NA | miR-215-5p | GC | qRT-PCR | ExoQuick kit | serum | 118 | 60 | 70/48 | I—IV | OS, DFS |
OS: R-Multi/ R-Uni DFS: E |
NA | 97.1 | 68.6 | 0.866 | good |
| Zhu L. 2022 [61] | China 2020–2021 | miR-552-5p | GC | qRT-PCR | UC | plasma | 30 | 56 | 16/14 | I—IV | NA | NA | NA | NA | NA | NA | good |
| Yang J. 2022 [62] | China NA |
miR-195-5p miR-211-5p |
GC | RT-qPCR | UC | plasma | 108 |
62.4 ± 8.9 62.2 ± 9.4 |
80/28 79/27 |
I—IV | NA | NA | NA | NA | NA |
0.745 (0.584–0.906) 0.798 (0.656–0.940) |
good |
| Chen S. 2022 [63] |
China NA |
miR-34a | HCC | qRT-PCR | UC | serum | 60 | 55 | 60/60 | I—IV | OS | R-Multi/ R-Uni | 6–60 | 51.7 | 78.3 | 0.664 (0.572–0.747) | good |
| Huang C. Y. 2021[64] |
China 2017–2018 |
let-7e miR-18a miR-27b miR-221 miR-20b miR-652 |
HCC | RT-qPCR | UC | plasma | 40 | 68 | 13/7 | NA | OS, DFS |
OS: R-Uni DFS: R-Uni |
80 | NA | NA | NA | poor |
| Hao Y. J. 2022 [65] | Taiwan 2019–2020 | miR-21 | CRC | qRT-PCR | Exosome isolation kit | plasma | 113 | 65 | 77/36 | I—IV | DFS, PFS | E | NA | NA | NA | NA | poor |
| Down-regulationa | |||||||||||||||||
| Soeda N 2019 [35] | Japan 2006–2015 | miR-92a | GC | qRT-PCR | UC | plasma | 129 | 68 | 90/39 | II—III | OS, RFS |
OS: R-Multi/ R-Uni RFS: E |
40.8 | 60.7 | 63.0 | NA | good |
| Yan S. 2017 [66] | China 2008–2014 | miR-638 | CRC | qRT-PCR | Exosome isolation kit | serum | 192 | 58 | 108/84 | I—IV | OS, DFS |
OS: R-Multi/ R-Uni DFS: E |
47 | NA | NA | NA | poor |
| Yan S. S. 2018 [67] | China 2012–2014 | miR-6869-5p | CRC | qRT-PCR | Exosome Isolation Kit | serum | 142 | 59 | 85/57 | I—IV | OS | R-Multi/ R-Uni | 36 | NA | NA | NA | good |
| Zou S. L. 2019 [68] | China NA | miR-150-5p | CRC | qRT-PCR | ExoQuick kit | serum | 133 | 60 | 49/84 | I—IV | OS, DFS |
OS: R-Multi/ R-Uni DFS: E |
60 | 76.1 | 81.0 | 0.870 | poor |
| Zhang N. 2020 [69] | China NA | miR-874 | CRC | RT-qPCR | Exosome Isolation kit | serum | 125 | 60 | 76/49 | I—IV | OS | R-Multi/ R-Uni | NA | 78.6 | 80.8 | 0.818 | poor |
| Liu C. 2016 [70] | China 2006–2011 | miR-4772-3p | CRC |
qRT-PCR RNA-seq |
ExoQuick kit | serum | 84 | 57 | 53/31 | II—III | OS | R-Multi | 51 (range: 45–64) | 77.1 | 78.6 | 0.720 (0.590–0.850) | poor |
| Hao X. 2020 [71] | China 2012–2013 | miR-320a | HCC | qRT-PCR | ExoQuick kit | serum | 104 | 60 | 77/27 | I—IV | OS, DFS |
OS: R-Multi/ R-Uni DFS: E |
NA | 80.0 | 77.9 | 0.860 | good |
| Jiao C. W. 2017 [72] | China 2007–2015 |
miR-34 s panel miR-34a miR-34b miR-34c |
HB | qRT-PCR | ExoQuick kit | serum | 89 | NA | 52/37 | I—IV | DFS | R-Multi/ R-Uni | 54 | NA | NA |
0.831(0.071–0.371) 0.813(0.023–0.296) 0.837(0.004–0.342) |
good |
| Li W. 2020 [73] | China NA | miR-320d | HCC | qRT-PCR | Exosome isolation kit | serum | 110 | 60 | 98/12 | I—IV | OS, DFS |
OS: R-Multi DFS: E |
NA | NA | NA | 0.869 | good |
| Liu W. F. 2017 [74] | China 2012 | miR-125b | HCC | qRT-PCR | ExoQuick kit | serum | 128 | 50 | 110/18 | I—III | OS | R-Multi/ R-Uni | 2.9–52.4 | 53.4 | 82.5 | 0.702 (0.602–0.802) | good |
| Sheng L. Q. 2020 [75] | China 2017–2018 |
miR-455-5p miR-30c-5p |
HCC | exomiRs sequencing | Exosome isolation kit | plasma |
cohort1:24 cohort2:27 |
NA |
cohort1:36/8 cohort2:8/4 |
N/A | OS | E | NA | NA | NA | NA | poor |
| Shi M. 2018 [76] | China 2008–2011 | miR-638 | HCC | qRT-PCR | Exosome isolation kit | serum | 126 | 65 | 70/56 | I—IV | OS | R-Multi/ R-Uni | 81.5 | NA | NA | NA | good |
| Suehiro T. 2018 [76] | Japan 2006–2013 | miR-122 | HCC | qRT-PCR | ExoQuick kit | serum | 75 | 73 | 49/26 | NA | DFS | R-Multi | 47 | NA | NA | NA | poor |
| Kumata Y. 2018 [77] | Japan 2006–2013 | miR-23b | GC | qRT-PCR | UC | plasma | 232 | NA | 165/67 | I—IV | OS, DFS |
OS: R-Multi/ R-Uni DFS: R-Multi/ R-Uni |
45.6 (range: 4.8–127.2) | NA | NA | NA | poor |
| Peng Z. Y. 2018 [78] | China 2008–2014 | miR-548c-5p | CRC | qRT-PCR | Exosome isolation kit | serum | 108 | 58 | 61/47 | I—IV | OS | R-Multi/ R-Uni | 44 | NA | NA | NA | poor |
| Zheng G-D. 2021 [79] | China 2008–2011 | miR-590-5p | GC | qRT-PCR | UC | serum | 168 | 60 | 117/51 | I—IV | OS | R-Multi/ R-Uni | 64.2 (range: 43.3–92) | 86.0 | 63.7 | 0.810 (0.751–0.860) | good |
GC Gastric Cancer, CRC Colorectal Cancer, LARC Locally Advanced Rectal Cancer, HCC Hepatocellular Carcinoma, HB Hepatoblastoma, PC Pancreatic Cancer, PDAC Pancreatic Ductal Adenocarcinoma, UC Ultracentrifuge, microRNA miR, NA Not Applicable, OS Overall Survival, DFS Disease Free Survival, PFS Progression Free Survival, RFS Relapse Free Survival, E Estimated, R-Multi Reported Multivariate, R-Uni Reported Univariate, qRT-PCR quantitative real-time PCR, RT-qPCR Reverse transcription quantitative PCR, Sen Sensitivity, Spec Specificity, AUC Area Under Curve.
aThe up- and down-regulation of exomiR(s) has been reported in comparison with the control group