High hypoxia inducible factor-1α expression is associated with reduced survival in patients with breast cancer: A meta-analysis

Table 4 Subgroup analysis of hypoxia-inducible factor 1α and disease-free survival in breast cancer patients

Stratified analysis	Number of studies	Pooled HR ratio (95%CI)	I2 statistic (%)	χ2 P value for heterogeneity	Analytical model	χ2 P value for subgroup differences
Age median
≤ 53[18,20,33,40,45,46,49,51-53]	10	1.32 (1.18-1.47)	74	< 0.001	REM	-
>53[15,16,19,27,29,30,32,34,41,50]	10	1.35 (1.20-1.53)	76	< 0.001	REM	0.74
Location
Asia[15,18,19,43-47,49-53]	13	1.37 (1.23-1.53)	80	< 0.001	REM	-
Europe[14,16,20,21,27-30,32-37,40,41]	16	1.73 (1.45-2.07)	60	0.001	REM	0.51
Antibody
H1α67[29,32,33,40,43,47]	6	1.61 (1.38-1.87)	63	0.02	REM	-
EP1215Y[49,52]	2	3.34 (1.90-5.90)	0	0.32	FEM	-
ESEE122[16,27,35]	3	1.79 (1.36-2.34)	0	0.82	FEM	-
ab51608[18,45]	2	1.23 (1.03-1.47)	90	0.002	REM	-
H206[34]	1	1.12 (0.96-1.31)	NA	-	-	-
MAB5382[53]	1	1.01 (0.81-1.26)	NA	-	-	-
NB100- 123H2[37]	1	1.27 (1.00-1.61)	NA	-	-	-
ab85886[50]	1	4.76 (2.17-10.44)	NA	-	-	-
Antiserum 2087[30]	1	4.20 (2.10-8.40)	NA	-	-	0.0004
Cut-off value
Percentage ≥ 1%[14,28,30,37,44,49]	6	1.70 (1.40-2.05)	73	0.002	REM	-
Percentage ≥ 5%[20,27,32,34,43,50,52]	7	1.36 (1.19-1.55)	81	< 0.001	REM	-
Scoring ≥ 1[16,18,19,29,35,36,41,45,51]	9	1.40 (1.21-1.61)	60	0.01	REM	-
Scoring ≥ 3[15,33,40,46,47,53]	6	1.31 (1.15-1.48)	78	0.0005	REM	0.25
Study design
Retrospective[19,30,34,45,47,50]	6	1.42 (1.25-1.62)	88	< 0.01	REM	-
Prospective[20,27,33,35,37,40]	6	1.46 (1.28-1.66)	8	0.37	FEM	0.79
Recruitment period
Before 2013[14-16,21,28-30,32-37,40,41,43,47,49,52,53]	19	1.37 (1.26-1.48)	73	< 0.001	REM	-
After 2013[18-21,27,44-46,50,51]	10	1.29 (1.15-1.44)	71	0.0003	REM	0.63
Grading
G1/G2 < 65%[19,20,29,32,35-37,40,44,45]	10	1.63 (1.40-1.89)	37	0.12	FEM	-
G1/G2 ≥ 65%[16,28,30,41,43,47,52,53]	8	2.25 (1.47-3.45)	82	< 0.001	REM	0.35
Staging
I/II < 70%[18,20,49,51]	4	1.22 (1.01-1.47)	76	0.005	REM	-
I/II ≥ 70%[15,43,45,50]	4	1.65 (1.33-2.05)	79	0.003	REM	0.85
Molecular typing
TNBC[19,44,45]	3	1.79 (1.03-3.11)	72	0.03	REM	-

HR: Hazard ratio; CI: Confidence interval; TNBC: Triple negative breast cancer; FEM: Fixed-effects model; REM: Random-effects model.