Table 1.
Basic characteristics of the included studies
| Author/ year |
Age (High/ Low) |
Country | Tumor type | Tumor size (High/Low) | Sample size | Male (High/Low) Female (High/Low) |
TNM Stage (High/Low) |
HIF-1α Expression | Survival analysis | Hr (95% CI) |
Method | Sample type | NOS score | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| High | Low | ||||||||||||||||||||
| Total | LNM | DM | Total | LNM | DM | ||||||||||||||||
| Jiang 2019 |
≥61(39-24) <61(43-18) |
China | GC | ≥6cm (50/33) <6cm(32/9) |
124 | 63/33 19/9 |
I/II (28/24) III/IV(54/18) |
82 | 59 | - | 42 | 24 | - | OS | 4.60 (2.45-8.66) |
IHC/ RT PCR |
T | 8 | |||
| Zhang 2018 | ≥60(113/116) <60(106/93) |
China | GC | ≥5cm (100/85) <5cm(119/124) |
428 | 155/149 64/60 |
I/II(95/119) III(144/90) |
219 | 151 | 32 | 209 | 98 | 14 | OS/ DFS |
OS: 0.65(0.50-0.85) DFS:0.67(0.52-0.88) |
IHC | T | 8 | |||
| Wang 2018 | ≥55(87/89) <55(136/101) |
China | HCC | ≥5cm (89/52) <5cm(126/133) |
419 | 157/66 151/39 |
I (91/98) II/III (132/92) |
223 | - | - | 190 | - | - | OS | 2.10 (1.35-3.26) |
IHC | T | 8 | |||
| Dai 2018 |
≥50(23/40) <50(16/11) |
China | HCC | ≥5cm(19/21) <5cm(19/30) |
90 | 35/49 4/2 |
- | 39 | - | - | 51 | - | - | OS | 3.109 (1.576-6.131) | IHC | T | 8 | |||
| Saka 2017 |
≥50(68/65) <50(23/30) |
Turkey | CRC | ≥5cm (44/55) <5cm(47/40) |
186 | 57/43 34/52 |
I/II (29/33) III/IV (62/62) |
91 | 53 | 44 | 95 | 56 | 52 | OS | - | IHC | T | 8 | |||
| Chen 2014 |
≥60(117/105) <60(100/124) |
China | GC | ≥5cm (122/131) <5cm (95/98) |
446 | 172/176 45/53 |
I/II(61/71) III/IV(156/158) |
217 | 173 | 63 | 229 | 176 | 25 | OS/ DFS |
OS: 3.53(2.66-4.66) DFS: 2.77(2.14-2.6) |
IHC | T | 8 | |||
| Lu 2013 |
≥49.82(25/18) <49.82(11/14) |
China | GC | ≤5cm (9/15) >5cm (27/17) |
68 | 21/22 15/10 |
I/II(10/16) III/IV(26/16) |
36 | 27 | 9 | 32 | 20 | 6 | *OS | 1.93 (0.65-5.75) | IHC | T | 8 | |||
| Yang 2013 |
≥50(52/40) <50(20/14) |
China | HCC | ≥5cm(40/26) <5cm(32/28) |
126 | 5/105 2/14 |
NR | 72 | - | - | 54 | - | - | OS/DFS | 2.82 (1.63-4.90) | IHC | T | 8 | |||
| Shimomura 2013 |
≥61(10/25) ≤60(10/19) |
Japan | CRC | ≥3cm(10/22) <3cm(13/32) |
64 | 11/31 9/13 |
16/25 | 20 | - | - | 44 | - | - | OS/DFS | OS: 1.34 (0.62-2.88) DFS: 2.09 (1.09-4) |
IHC | T | 8 | |||
| Xie 2013 |
≤60(12/17) >60(16/15) |
China | CRC | ≤2cm (6/18) >2cm (22/14) |
60 | 21/19 7/13 |
I/II(13/13) III/IV(15/19) |
28 | 16 | - | 32 | 11 | - | OS | 1.550.60-4.01) | IHC | T | 8 | |||
| Isobe 2013 |
≥65(48/30) <65(36/14) |
Japan | GC | NR | 128 | 56/35 28/9 |
NR | 84 | 50 | 20 | 44 | 12 | 2 | OS | 6.92(1.24-130.4) | IHC | T | 8 | |||
| Xiang 2012 | ≤50(19/17) >50(11/22) |
China | HCC | ≤5cm (18/15) >5cm (12/24) |
69 | 27/34 3/5 |
I/II(15/23) III/IV(15/16) |
30 | 21 | - | 39 | 23 | - | OS | 2.02 (1.12-3.66) |
IHC | T | 8 | |||
| Ogawa 2011 | ≥60(7/7) <60(4/4) |
Japan | EsoC | NR | 37 | 10/14 1/0 |
NR | 11 | 9 | 4 | 14 | 8 | 1 | RFS | 0.071 (0.015-0.34) | IHC | T | 8 | |||
| Shioya 2011 | NR | Japan | CRC | NR | 50 | 38 | NR | 21 | 17 | - | 29 | 18 | - | RFS | 4.13 (1.52-11.24) | IHC | T | 8 | |||
| Munipalle 2011 | >70(13/5) <70(6/12) |
UK | EsoCl | NR | 36 | 8/7 11/10 |
I/II (4/3) III/IV (17/12) |
19 | 14 | 8 | 17 | 13 | 4 | OS | 0.92 (0.67-1.31) | IHC | T | 8 | |||
| Ogane 2010 | ≤62(15/31) >62(34/16) |
Japan | EsoC | NR | 96 | 60/29 5/2 |
NR | 65 | 35 | - | 31 | 9 | - | OS/DFS | OS:2.92(1.16-7.32) DFS:3.12(1.28-8.63) |
IHC | T | 8 | |||
| Saigusa 2010 | ≥65 | Japan | CRC | NR | 52 | 42/10 | NR | - | - | - | - | - | - | OS | OS : 4.36(0.05-0.91) | IHC/RT-PCR | T | 8 | |||
| Kwon 2010 | - | Korea | CRC | ≥5cm (42/56) <5cm (21/29) |
311 | 109/62 87/53 |
I/II (100/73) III/IV (96/42) |
63 | - | - | 85 | - | - | *OS/DFS | OS:2.43(1.39-4.21) DFS:1.71(0.98-2.99) |
IHC | T | 8 | |||
| Baba 2010 |
≥70(53/223) <70(89/366) |
USA | CRC | NR | 731 | 41/220 101/369 |
I/II (42/180) III/IV (74/234) |
142 | - | - | 589 | - | - | OS | 1.50 (1.16-1.94) |
IHC | T | 8 | |||
| Qiu 2010 |
≤60(58/41) >60(52/37) |
China | GC | ≤5cm (36/52) >5cm (74/23) |
188 | 72/55 38/23 |
I/II(41/56) III/IV(69/22) |
110 | 82 | - | 74 | 44 | - | OS | 2.26(1.47-3.48) | IHC | T | 8 | |||
| Dai 2009 |
≤52(26/28) >52(16/40) |
China | HCC | ≤5cn (21/35) >5cm (28/38) |
110 | 38/57 4/11 |
I/II(18/40) III/IV(24/28) |
42 | - | - | 68 | - | - | OS/DFS | OS: 0.47(0.25-0.89) DFS: 0.44(0.25- 0.8) |
IHC/ RT-PCR | T | 8 | |||
| Chen 2009 |
<60(17/13) ≥60(8/16) |
China | EsoC | NR | 54 | 15/23 10/6 |
I/II(5/17) III/IV(20/12) |
25 | 16 | - | 29 | 12 | - | *OS | 1.71(0.57-5.13) | IHC | T | 8 | |||
| Cao 2009 |
≥60(24/23) <60(15/9) |
China | CRC | ≥5cm (22/18) <5cm (1714) |
71 | 24/19 15/13 |
I/II(15/27) III/IV(24/5) |
39 | 22 | 10 | 32 | 5 | 1 | OS | 2.69(1.15-6.30) | IHC | T | 8 | |||
| Jubb 2009 | NR | Australia | CRC | NR | 164 | NR | NR | 95 | - | - | 60 | - | - | OS | 1.61(1.01-2.57) | IHC | T | 8 | |||
| Rajaganesh2009 | NR | UK | CRC | NR | 55 | NR | NR | 25 | - | - | 30 | - | - | *DFS | 6.8(3.11-14.85 | IHC | T | 8 | |||
| Schemitz 2009 | NR | German | CRC | NR | 135 | NR | I/II (9/38) III/IV(24/48) |
34 | 22 | 13 | 90 | 43 | 16 | OS | 1.76(0.99-3.22) | IHC | T | 8 | |||
| Rasheed 2009 | NR | UK | CRC | NR | NR | 32/24 16/18 |
I/II(258/32) III/IV(23/10) |
48 | 23 | - | 42 | 10 | - | OS/DFS | 4.11(1.37-12.35) 4.47 (1.68-11.89) |
IHC | T | 8 | |||
| Oh 2008 | ≥60(9/47) <60(9/49) |
Korea | GC | ≥4cm (14/53) <4cm (4/43) |
114 | 10/57 8/39 |
I/II(74/60) III/IV(11/34) |
18 | 15 | - | 96 | 58 | - | OS | 4.08(1.88-8.88) | IHC | T | 8 | |||
| Kolev 2008 | ≥60(49/26) <60(46/31) |
Japan | GC | ≥5cm (48/24) <5cm (47/33) |
152 | 72/38 23/19 |
I/II(62/42) III/IV(35/15) |
95 | 50 | - | 57 | 21 | - | OS/ DFS |
0.88(0.48-1.62) 1.02(0.5-2.07) |
IHC | T | 8 | |||
| Tzao 2008 | ≤70(36/24) >70(16/9) |
China | EsoC | NR | 85 | 47/33 5/0 |
I/II(25/23) III/IV(27/10) |
52 | 29 | 13 | 33 | 12 | 4 | OS | 1.77(1.05-2.97) | IHC | T | 8 | |||
| Ma 2007 | NR | China | GC | NR | 118 | NR | NR | 58 | 50 | 47 | 60 | 33 | 8 | OS | 7.51(4.30-13.11) | IHC | T | 8 | |||
| Griffiths 2007 | NR | UK | GC | NR | 80 | NR | I/II(41/44) III/IV(51/37) |
93 | 64 | 2 | 83 | 60 | 2 | OS | 1.10(0.8-1.4) | IHC | T | 8 | |||
| SUN 2007 | ≥60(19/16) <60(7/16) |
USA | PDAC | ≥2cm (25/25) <2cm (1/7) |
58 | 16/21 10/11 |
I/II(10/26) III/IV(16/6) |
26 | 12 | - | 32 | 6 | - | OS | 2.22(1.00-4.99) | IHC | T | 8 | |||
| Sumiyoshi 2006 | NR | Japan | GC | NR | 216 | 56/92 29/39 |
I/II (45/80) III/IV(40/60) |
85 | 49 | 5 | 131 | 61 | 4 | OS | 2.19(1.39-3.47) | IHC | T | 8 | |||
| Zhang 2007 | >63(18/8) ≤63(16/10) |
China | EsoC | NR | 50 | 27/10 7/6 |
NR | 34 | 31 | 7 | 16 | 10 | 0 | *OS | 4.01(1.69-9.51) | IHC | T | 8 | |||
| Urano 2006 | NR | Japan | GC | NR | 146 | NR | I/II(46/25) III/IV(43/32) |
83 | 36 | - | 55 | 28 | - | *OS | 0.96(0.42-2.20) | IHC | T | 8 | |||
| Lu 2006 | NR | China | CRC | NR | 30 | NR | NR | 19 | 12 | - | 11 | 0 | - | *OS | 9.54(1.18-70.66) | IHC | T | 8 | |||
| Theodoropoulos 2006 | ≤68(24/20) >68(20/28) |
Greece | CRC | >3cm (36/39) <3cm (8/9) |
92 | 24/31 20/17 |
NR | 44 | 30 | - | 48 | 21 | - | OS/DFS | OS:3.65(1.52-8.81) DFS: 3.46(1.32-9.8) |
IHC | Tissue | 8 | |||
| Mizokami 2006 | ≥65(20/46) <65(29/31) |
Japan | GC | ≥3cm (39/42) <3cm (10/35) |
126 | 35/50 14/27 |
NR | 49 | 25 | - | 77 | 26 | - | OS | 2.09 (1.08-4.06) |
IHC | Tissue | 8 | |||
| Katsuta 2005 | NR | Japan | EsoC | NR | 48 | 24/11 10/3 |
I (16/9) II/III/IV(18/5) |
34 | 15 | 4 | 14 | 2 | 1 | *OS | 1.19(0.4-5.39) | IHC / RT-PCR |
Tissue | 8 | |||
| Yoshimura 2004 | NR | Japan | CRC | NR | NR | 19/32 20/16 |
I/II(12/16) III/IV(27/32) |
39 | 14 | - | 48 | 20 | - | *OS | 2.56(1.19-5.50) | IHC | Tissue | 8 | |||
| Kimura 2004 | ≤60(10/19) ≥61(22/31) |
Japan | EsoC | NR | 82 | 31/41 1/9 |
I/II(9/21) III/IV(23/29) |
32 | 20 | - | 50 | 30 | - | *OS | 1.59(0.86-2.97) | IHC/ RT.PCR |
Tissue | 7 | |||
| Kurokawa 2003 | <60(26/18) ≥60(64/22) |
Japan | EsoC | >4.5cm (47/23) <4.5cm (43/17) |
130 | 79/34 11/6 |
I/II(64/17) III/IV(26/23) |
90 | 38 | 11 | 40 | 28 | 11 | OS | 1.54(0.84-2.84) | IHC | Tissue | 8 | |||
| Kuwai 2003 | NR | Japan | CRC | ≥5cm (39/21) <5cm (42/37) |
139 | NR | NR | 81 | 46 | 21 | 58 | 24 | 5 | *OS | 1.53 (0.46-5.13) | IHC | Tissue | 7 | |||
Abbreviations: Hr: Hazard ratio, CI: Confidence interval, NOS: Newcastle-Ottawa Scale, UK: united kingdom, USA, Unites states of America, GC: Gastric Cancer, HCC: Hepatocellular carcinoma, CRC: Colorectal cancer, EsoC; Esophageal cancer, PDAC: Pancreatic ductal adenocarcinoma, OS: overall survival, DFS: Disease free survival, LNM: lymph node metastasis, DM: distant metastasis. IHC: immunohistochemistry, RT-PCR: real time-PCR, T: Tissue, NR: not reported, Note: The dashes represent no data.