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 |