Table 3.
Subgroup analysis of the included studies.
| Subgroup analyses | No. | Case/control | Sensitivity (95% CI) | Specificity (95% CI) | PLR (95% CI) | NLR (95% CI) | DOR (95% CI) | |
|---|---|---|---|---|---|---|---|---|
| Ethnicity | America | 4 | 203/94 | 0.79 (0.72–0.84) | 0.74 (0.64–0.83) | 2.92 (2.11–4.20) | 0.29 (0.21–0.38) | 10.32 (5.92–18.01) |
| Asia | 41 | 3685/1493 | 0.55 (0.53–0.56) | 0.77 (0.74–0.79) | 2.70 (2.09–3.50) | 0.40 (0.30–0.52) | 7.64 (4.70–12.41) | |
| Europe | 30 | 2295/850 | 0.70 (0.68–0.72) | 0.76 (0.73–0.79) | 3.92 (2.72–5.66) | 0.28 (0.21–0.39) | 20.24 (10.10–40.57) | |
| Cancer type | DSC | 44 | 3366/1252 | 0.65 (0.64–0.67) | 0.79 (0.77–0.81) | 3.62 (2.68–4.90) | 0.27 (0.19–0.38) | 15.69 (8.99–27.41) |
| ESC | 10 | 994/299 | 0.55 (0.52–0.58) | 0.70 (0.64–0.76) | 2.66 (1.24–5.73) | 0.54 (0.39–0.74) | 5.57 (1.70–18.25) | |
| NSC | 3 | 84/107 | 0.85 (0.76–0.92) | 0.80 (0.71–0.87) | 4.40 (1.67–11.63) | 0.17 (0.01–0.28) | 26.31 (6.92–99.99) | |
| RSC | 10 | 1258/372 | 0.49 (0.46–0.51) | 0.69 (0.64–0.74) | 1.79 (1.26–2.54) | 0.52 (0.36–0.75) | 4.04 (1.88–8.70) | |
| USC | 8 | 483/407 | 0.76 (0.72–0.80) | 0.76 (0.71–0.80) | 3.40 (2.22–5.20) | 0.32 (0.25–0.39) | 12.36 (6.49–23.57) | |
| Specimen | Urine | 9 | 345/289 | 0.79 (0.74–0.83) | 0.82 (0.77–0.86) | 5.50 (2.78–10.90) | 0.29 (0.20–0.42) | 26.19 (9.26–74.10) |
| Serum | 47 | 3804/1617 | 0.66 (0.64–0.67) | 0.77 (0.74–0.79) | 3.43 (2.60–4.54) | 0.29 (0.22–0.38) | 14.22 (8.30–24.37) | |
| Plasma | 16 | 1991/456 | 0.50 (0.47–0.52) | 0.72 (0.67–0.76) | 1.87 (1.42–2.45) | 0.58 (0.47–0.72) | 3.64 (2.21–5.93) | |
| Other | 3 | 43/75 | 0.67 (0.52–0.81) | 0.73 (0.62–0.83) | 2.83 (1.09–7.35) | 0.44 (0.28–0.68) | 7.24 (1.84–28.49) | |
| Age | < = 60 | 20 | 2216/772 | 0.58 (0.56–0.6) | 0.73 (0.7–0.76) | 2.52 (1.91–3.32) | 0.42 (0.32–0.53) | 7.05 (4.15–11.97) |
| >60 | 33 | 2013/934 | 0.65 (0.63–0.68) | 0.77 (0.74–0.8) | 3.16 (2.32–4.31) | 0.3 (0.21–0.42) | 13.48 (7.27–25) | |
| Therapy | SURG | 18 | 1560/386 | 0.68 (0.66–0.71) | 0.79 (0.75–0.83) | 3.42 (2.39–4.91) | 0.26 (0.17–0.41) | 15.52 (7.43–32.42) |
| SURG + CT* | 16 | 1248/461 | 0.71 (0.68–0.73) | 0.77 (0.73–0.8) | 3.49 (2.29–5.3) | 0.33 (0.24–0.44) | 14.39 (6.86–30.17) | |
| SURG + CT + RT | 9 | 862/227 | 0.44 (0.41–0.47) | 0.81 (0.75–0.86) | 2.77 (1.68–4.58) | 0.48 (0.34–0.69) | 6.3 (2.62–15.13) | |
| Type of EVs** | lEVs | 41 | 5064/1681 | 0.57(0.56–0.59) | 0.76(0.73–0.78) | 2.67(2.10–3.34) | 0.39(0.31–0.51) | 8.42(5.34–13.28) |
| sEVs | 34 | 1119/756 | 0.67(0.65–0.69) | 0.81(0.75–0.85) | 3.71(2.62–5.25) | 0.29(0.22–0.40) | 14.61(7.71–27.68) | |
| EVs purification | Isolation kit*** | 26 | 2074/875 | 0.56(0.53–0.58) | 0.73(0.7–0.76) | 2.52(1.9–3.34) | 0.4(0.31–0.53) | 7.41(4.31–12.74) |
| UC# | 49 | 4109/1562 | 0.65 (0.63–0.66) | 0.78(0.76–0.8) | 3.51(2.66–4.64) | 0.31(0.24–0.41) | 13.92(8.3–23.34) | |
| EVs identification | NA | 11 | 703/312 | 0.56 (0.52–0.6) | 0.78(0.73–0.83) | 2.59(1.44–4.68) | 0.36(0.14–0.89) | 8.13(2.64–25.06) |
| Microscopic## | 31 | 2579/1075 | 0.54 (0.52–0.56) | 0.72(0.69–0.75) | 2.61(1.98–3.43) | 0.41(0.32–0.53) | 8.2(4.61–14.6) | |
| Exosomal surface biomarkers### | 20 | 1817/378 | 0.68(0.66–0.7) | 0.8(0.77–0.83) | 3.6(2.09–6.18) | 0.26(0.13–0.51) | 14.86(8.36–26.41) | |
| Quantification and size determination& | 13 | 1084/672 | 0.74 (0.71–0.76) | 0.82(0.77–0.85) | 4.35(2.85–6.62) | 0.31(0.24–0.41) | 16.37(5.91–45.3) | |
| EVs secretion level | Increase | 62 | 5123/2095 | 0.63 (0.61–0.64) | 0.77(0.76–0.79) | 3.22(2.61–3.98) | 0.32(0.26–0.4) | 12.31(8.19–18.5) |
| Decrease | 11 | 1032/302 | 0.56 (0.53–0.59) | 0.69(0.63–0.74) | 1.99(1.2–3.3) | 0.58(0.41–0.81) | 4.21(1.73–10.23) | |
EVs, extracellular vesicles; DSC, digestive system cancer; ESC, endocrine system cancer; NSC, neuron system cancer; RSC, respiratory system cancer; USC, urinary system cancer; SURG, surgery; CT, chemotherapy; RT; Radiotherapy; lEVs, large EVs; sEVs, small EVS; UC, ultracentrifuge.
Neoadjuvant chemotherapy and adjuvant therapy are categorized as chemotherapy.
EVs sedimenting at 100,000 × g into is categorized as a small EVs (sEVs) and EVs sedimenting at 2,000 × g is categorized as a large EVs (lEVs, large fragments of cells, large apoptotic bodies) (Mateescu et al., 2017; Slomka et al., 2018).
Isolation kit refer to the standard total extracellular vesicles isolation kit media and urine for biomarker analysis.
Using the differential ultracentrifugation range (>100,000 ×g (100,000–200,000 ×g) for 2 h) for isolation of different exosome isolation methods yield different amount of exosomes (Patel et al., 2019).
Microscopic methods for EVS identification is contended the transmission electron microscope, atomic force microscopy and selected reaction monitoring methods.
CD81, CD63, CD64, CD65, and CD66 are a cell surface glycoprotein exosomal cell surface markers that is using mostly for isolation isolating exosomes from tissue culture media and urine for biomarker analysis (Konoshenko et al., 2018).
Quantificative methods for EVS identification is the quantificative and size determination based on the western blot and ELISA.