Table 1.
Main characteristics of the studies included in the meta-analysis
| Authors year | CSC markers | Country duration | Mean/median age (month) | Sample size (n) | Gender (M/F) | TNM stage | Cut-off value | Follow-up (month) | Outcome | Hazard ratio (HR) | NOS score# |
|---|---|---|---|---|---|---|---|---|---|---|---|
|
Wang 2011 [18] |
CD44, CD133 |
Singapore 2000–2004 |
64 | 116 | 76/36 | I–IV |
CD44: 5 score (0–300) CD133: 50 score (0–300) |
110 | OS | E | 8 |
|
Wakamatsu 2012 [19] |
CD44, CD133, ALDH1 |
Japan NR |
65 | 190 | NR | I–IV | > 10% | 83 | OS |
CD44, CD133: R-Multi ALDH1: R-Uni |
6 |
|
Chen 2013 [20] |
CD44, CD133 |
China 2000–2005 |
55 (23 to 84) | 152 | 101/51 | I–IV |
CD44: > 65% CD133: > 50% |
48.6 (1.0–76.7) | OS, DFS |
OS: R-Multi DFS: E |
9 |
|
Cao 2014 [21] |
CD44 |
China 2005–2007 |
60.5 (33–88) | 203 | 140/63 | NR | > 10% | 66 (7–108) | OS | E | 6 |
|
Cao 2014 [22] |
CD44, CD24 |
China 2000–2010 |
64 (32 to 87) | 290 | 221/69 | I–IV | ≥ 30 (0–300) | 41(3–135) | OS | R-Multi | 9 |
|
Jian-Hui 2016 [23] |
CD44, Gli-1, Shh |
China 2006 |
60 | 101 | 62/39 | I–III | ≥ 4 score (0–12) | 90 | OS, DFS |
CD44, Shh: R-Uni Gli: R-Multi |
8 |
|
Zhang 2016 [24] |
CD44, CD133, Sox-2, Oct-4, Gli-1 |
China 2005–2011 |
NR | 101 | NR | I–IV | > 10% | 80 | OS | E | 6 |
|
Kodama 2017 [25] |
CD44, CD44v6, CD44v9 |
Japan 2007–2009 |
70 (38–91) | 123 | 83/40 | I–IV | > 5% | 68 (1–97) | DSS | R-Uni | 7 |
|
Senel 2017 [26] |
CD44, ALDH1 |
Turkey 2011–2015 |
NR | 80 | 48/32 | I–III | > 1 score (0–3) | 60 | DFS | E | 7 |
|
Sun 2017 [27] |
CD44 |
China 2004–2012 |
60 | 200 | 135/65 | I–IV | > 3 score (0–6) | 110 | OS | E | 8 |
|
Tongtawee 2017 [28] |
CD44 |
Thailand 2011–2015 |
61.38 ± 12.39 | 162 | 117/45 | I–IV | > 0 score (0–3) | 60 | OS | R-Multi | 8 |
|
Ryu 2018 [29] |
CD44 |
Korea 1998–2009 |
60.7(27–84) | 143 | 91/52 | NR | > 2 score (0–3) | 45 (0–155) | OS, DFS | R-Multi | 7 |
|
Ibrahim 2019 [30] |
CD44 |
Egypt 2012–2016 |
52.5(41–60) | 40 | 25/15 | I–III | > 10% | 8–36 | OS, DFS | R-Uni | 9 |
|
Xie 2015 [31] |
CD44v6 |
China 2006–2008 |
60 | 208 | 154/54 | I–IV | > 3 score | 80 | OS | R-Multi | 8 |
|
Xu 2017 [32] |
CD44v6 |
China 2006–2013 |
60 | 103 | 69/34 | I–IV | NR | 120 | OS | E | 7 |
|
Yamaguchi 2002 [33] |
CD44v6 |
Japan 1984–1993 |
NR | 201 | NR | I–IV | NR | 144 | OS | E | 6 |
|
Zheng 2017 [34] |
CD44v6 |
China 2010–2015 |
65 (43–80) | 49 | 39/10 | NR | NR | 33 (1–73) | DSS | R | 9 |
|
Hirata 2013 [35] |
CD44v9 |
Japan 2008–2010 |
67.5 (46–90) | 65 | 56/9 | NR | 3.58 ± 7.74% | 32 (1–36) | RFS | R-Multi | 7 |
|
Yamakawa 2017 [36] |
CD44v9 |
Japan 2011–2012 |
70 | 103 | 79/24 | I–IV | ≥ 4 score | 61.0 | RFS | R-Multi | 8 |
|
Go 2016 [37] |
CD44v9 |
Korea 1999–2007 |
24–85 | 333 | 218/115 | I–III | > 0 score (0–3) | 120 | OS | E | 8 |
|
Songun 2005 [38] |
CD44v9 |
Netherlands 1989–1993 |
64.7 (31–84) | 300 | 181 /119 | I–IV | ≥ 5% | 120 | OS | E | 6 |
|
Ishigami 2010 [39] |
CD133 |
Japan 2001–2003 |
65 (40 to 85) | 97 | 69/28 | I–IV | containing at least one CD133 positive cell | 60 | OS | E | 8 |
|
Yu 2010 [40] |
CD133 |
China 2004–2009 |
62.0 (29–83) | 99 | 69/30 | I–IV | NR | 26.76 ± 17.02 | OS | R-Multi | 8 |
|
Zhao 2010 [41] |
CD133 |
China NR |
58.1 (18–85) | 336 | 274/62 | I–IV | ≥ 5 score (0–12) | 120 | OS | E | 7 |
|
Lee 2012 [42] |
CD133 |
Korea 2001–2005 |
61.5 (29–89) | 100 | 71/29 | II–III | ≥ 6 score (0–12) | 46.9 (0–115) | OS, DFS | R-Multi | 8 |
|
Hashimoto 2014 [43] |
CD133 |
Japan 2004–2006 |
66 ± 11 | 189 | 133/56 | I–IV | > 5% | 60 | OS | E | 7 |
|
Zhou 2015 [44] |
CD133, LGR-5 |
China 2004–2006 |
59.6 (23–88) | 261 | 172/89 | I–IV | > 2 score (0–12) | 43.9 (0–110) | OS | R-Multi | 7 |
|
Lu 2017 [45] |
CD133 |
China 2010–2011 |
58.1 ( 28–78) | 236 | 159/77 | I–III | ≥ 3 score (0–12) | 48.6 (9–72) | OS | R-Multi | 7 |
|
Attia 2019 [46] |
CD133 |
Egypt 2012–2015 |
54.44 (24–81) | 77 | 45/32 | I–IV | > 3.5 score (0–6) | NR | RFS | R | 6 |
|
Liu 2019 [47] |
CD133, ALDH1 |
China 2012–2017 |
53 (32–76) | 91 | 69/22 | III | ≥ 5 score (0–12) | 27 (1–60) | OS, DFS |
OS: E DFS:R-multi |
7 |
|
Matsuoka 2012 [48] |
Sox-2, Oct-4, Nanog |
Japan NR |
NR | 290 | NR | I–IV | ≥ 5 score (0–5) | 120 | OS | R-Uni | 6 |
|
Li 2015 [49] |
SOX-2, Oct-4, Nanog |
China 2008–2009 |
55 (28–78) | 69 | 41/18 | I–III | ≥ 5 score (0–5) | 35(6–60) | OS, DFS | E | 8 |
|
Yang 2017 [50] |
Sox-2, ALDH1 |
China 2010–2013 |
63 (29–82) | 122 | 100/22 | I–IV | > 5% | 26 (1 to 75) | OS |
Sox-2: R-Multi ALDH1: R-Uni |
8 |
|
Zhang 2010 [51] |
Sox-2 |
China 2004 |
57.8 ( 29–79) | 50 | 35/15 | I–IV | > 10% | 1–50 | OS | E | 7 |
|
Camilo 2014 [52] |
Sox-2 |
Portugal 1988–2010 |
66.5 (24–89) | 201 | 124/77 | I–IV | > 5% | 250 | OS | E | 8 |
|
Kong 2014 [53] |
Oct-4 |
China NR |
60 | 158 | 104/54 | I–IV | > 0 score (0–3) | 60 | OS | R-Multi | 6 |
|
Jiang 2016 [54] |
Oct-4 |
China 2001–2010 |
62 (30–85) | 412 | 284/128 | I–IV | ≥ 4 score | 60 | OS | R-Multi | 7 |
| Javanbakht 2017 [55] | Oct-4 |
Iran 2010–2014 |
59.3 (37–85) | 40 | 16/24 | I–IV | > 25% | 50 | OS | R-Multi | 6 |
|
El-Guindy 2019 [56] |
Oct-4 |
Egypt 2015–2016 |
18–70 | 45 | 28/17 | I–III | ≥ 6 score (0–9) | 24 | OS, DFS | E | 6 |
|
Li 2014 [57] |
ALDH1 |
China 2005–2008 |
57.0 ( 22–82) | 216 | 140/76 | I–III | ≥ 2 score (0–3) | 27 (4–82) | OS, RFS | R-Multi | 8 |
|
41Lu 2018 [58] |
ALDH1 |
China 2011–2012 |
60 | 232 | 148/84 | I–III | > 2 score (0–12) | 48.7 (10–83) | OS | R-Multi | 7 |
|
Simon 2012 [59] |
LGR-5 |
Germany 1997–2009 |
68 + _11.4 | 487 | 304/183 | I–IV | NR | 60.9 (14.3–129.9) | OS | E | 6 |
|
Bu 2013 [60] |
LGR-5 |
China 2002–2007 |
61 (22–87) | 257 | 185/72 | I–IV | ≥ 3 score (0–6) | 60 | OS | R-Uni | 8 |
|
Xi 2014 [61] |
LGR-5 |
China 1999–2004 |
59.6 (24–86) | 318 | 254/59 | I–IV | ≥ 2 score (0–6) | 120 | OS | R-Multi | 7 |
|
Choi 2017 [62] |
LGR-5 |
Korea 2004–2006 |
60 | 456 | 312/144 | I–IV | NR | NR | CSS | R-Multi | 6 |
|
Liu 2019 [63] |
LGR-5 |
China 2009–2014 |
60 (33 to 85) | 100 | 68/32 | I–III | > 6 score (0–12) | 60 | OS | E | 8 |
|
Liu 2008 [64] |
Bmi-1 |
China 1999–2002 |
60 | 146 | 92/54 | I–IV | ≥ 10% | 48 | OS | R-Multi | 7 |
|
Zhang 2010 [65] |
Bmi-1 |
China NR |
60 | 75 | 50/25 | I–IV | ≥ 10% | 110 | OS | E | 7 |
|
Yang 2011 [66] |
Bmi-1 |
China 2004–2005 |
60 | 219 | 162/57 | I–IV | ≥ 20% | 29.57 (1.90–78.10) | DSS | E | 7 |
|
Wu 2016 [67] |
Bmi-1 |
China NR |
60 | 352 | 236/116 | I–IV | NR | 120 | OS | E | 6 |
|
Lu 2012 [68] |
Bmi-1 |
China 1993–2006 |
55 | 309 | 98/211 | NR | > 5% | 67.8 (2–200) | OS | E | 7 |
|
Lin 2012 [69] |
Nanog |
China NR |
50 | 105 | 71/34 | I–IV | > 2 score (0–12) | 60 | OS | R-Multi | 7 |
|
Chou 2007 [70] |
CD24 |
Taiwan 1995–1997 |
73 (40–99) | 103 | 75/28 | I–IV | > 10% | 86.5 (1–120) | OS | R-Multi | 6 |
|
Fujikuni 2014 [71] |
CD24 |
Japan 2001–2008 |
65 | 119 | 73/46 | I–III | > 1% | 60 | OS | E | 6 |
|
Darwish 2004 [72] |
CD24 |
Korea NR |
54.3 | 300 | 200/100 | I–IV | NR | 53 (1–72) | OS | R-Multi | 8 |
|
Bektas 2010 [73] |
CD24 |
Turkey 2001–2009 |
61.5 (30–84) | 93 | 59/34 | I–IV | > 10% | 36 (0–100) | OS | E | 8 |
|
Hu 2017 [74] |
Gli-1, Shh |
China NR |
60 | 90 | 53/37 | I–IV | ≥ 6 score (0–12) | 80 | OS | E | 6 |
|
Shao 2017 [75] |
Gli-1 |
China 2008–2010 |
60 | 67 | 50/17 | I–IV | ≥ 5 score (0–12) | 60 | OS | R-Multi | 9 |
|
Tang 2018 [76] |
Gli-1 |
China 2009–2010 |
60 | 90 | 68/22 | I–IV | > 3 score (0–9) | 80 | OS | R-Multi | 7 |
|
Ke 2020 [77] |
Gli-1, Shh |
China 2010–2013 |
60 | 128 | 128/50 | I–III | > 3 score | 120 | OS | R-Multi | 8 |
|
Wang 2014 [78] |
Gli-1 |
China 2005–2007 |
63 (46–83) | 121 | 92/29 | I–IV | ≥ 10% | 30 ( 5–60) | OS | R-Multi | 7 |
|
Yao 2019 [79] |
Gli-1 |
China 2010–2012 |
60 | 57 | 40/17 | I–IV | ≥ 5 score (0–12) | 60 | OS | E | 9 |
|
Ertao 2016 [80] |
Shh |
China 2004–2005 |
60 | 117 | 71/46 | I–IV | > 10% | 47.6 (3–114) | OS | R-Multi | 8 |
|
Kim 2012 [81] |
Shh |
Korea 2004–2007 |
NR | 319 | NR | I–IV | > 3 score (0–4) | 80 | OS | E | 6 |
|
Yoo 2011 [82] |
Shh |
Korea 2002–2004 |
60 | 178 | 124/49 | I–IV | NR | 60 | OS | E | 7 |
|
Niu 2014 [83] |
Shh |
China 2008–2009 |
54.37 (22–75) | 113 | 73/40 | I–IV | ≥ 2 score (0–3) | 43.6 (6–78) | OS | R-Multi | 7 |
HR: Hazard ratio; OS: Overall survival; RFS: Relapse-free survival; DSS: Disease-specific survival; DFS: Disease-free survival; CSS: Cancer-specific survival; NR: Not reported; IHC: Immunohistochemistry; E: Estimated by survival curve; R: Reported; R-Uni: Univariate analysis reported by article; R-Multi: Multivariate analysis reported by article; # Study quality was evaluated according to the Newcastle–Ottawa Scale (range, 1–9)