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

Table 3 Subgroup analysis of hypoxia-inducible factor 1α and overall 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[17,18,20,33,39,40,46,48,49,52,53]	11	1.35 (1.21-1.51)	76	< 0.00001	REM	-
≥ 53[12,13,15,19,27,29,30,32,34,38,54]	11	1.52 (1.33-1.74)	45	0.05	FEM	0.18
Location
Asia[15,18,19,22,42,43,46,48,49,52,53]	11	1.55 (1.39-1.73)	31	0.11	FEM	-
Europe[12,13,20,26,27,29-34,37-40,54]	16	1.58 (1.39-1.79)	29	0.14	FEM
Africa[17]	1	1.20 (1.02-1.41)	NA	-	-	0.002
Antibody
H1α67[29,32,33,40,43]	5	1.52 (1.26-1.83)	27	0.24	FEM	-
EP1215Y[17,31,49,52]	4	1.42 (1.22-1.64)	87	< 0.0001	REM	-
ab51608[18,22]	2	2.23 (1.37-3.64)	0	0.85	FEM	-
H206[34,39]	2	1.65 (1.21-2.25)	70	0.07	REM	-
NB100- 123H2[37]	1	1.21 (0.95-1.54)	NA	-	-	-
NB100- 131[38]	1	1.63 (1.03-2.58)	NA	-	-	-
BD610959[26]	1	1.61 (0.63-4.11)	NA	-	-	-
Ab82832[48]	1	0.23 (0.08-0.66)	NA	-	-	-
Antiserum 2087[30]	1	1.41 (1.12-1.77)	NA	-	-	-
MAB5382[53]	1	1.05 (0.81-1.36)	NA	-	-	-
ESEE122[27]	1	2.26 (1.06-4.82)	NA	-	-	0.16
Cut-off value
Percentage ≥ 1%[26,30,37,39,49]	5	1.49 (1.30-1.71)	72	0.006	REM	-
Percentage ≥ 5%[13,17,20,27,32,34,38,43,52]	9	1.36 (1.20-1.55)	59	0.01	REM	-
Scoring ≥ 1 [18,19,29,31,42,54]	6	1.21 (1.05-1.39)	69	0.007	REM	-
Scoring ≥ 3[12,15,22,33,40,46,48,53]	8	1.25 (1.06-1.47)	70	0.002	REM	0.71
Study design
Retrospective[12,19,30,34,38]	5	1.48 (1.23-1.77)	59	0.04	REM	-
Prospective[17,20,27,33,37,40]	6	1.27 (1.13-1.44)	26	0.24	FEM	0.18
Publish date
Before 2013[13,15,29,30,32-34,37,39,40,42,43,49,52-54]	16	1.32 (1.22-1.44)	68	< 0.0001	REM	-
After 2013[12,17-20,22,26,27,31,38,46,48]	12	1.35 (1.19-1.54)	64	0.001	REM	0.53
Grading
G1/G2 < 65%[13,17,19,20,29,32,37,39,40,54]	10	1.35 (1.21-1.50)	40	0.09	FEM	-
G1/G2 ≥ 65%[22,30,31,38,42,43,48,52,53]	9	1.19 (1.07-1.33)	71	0.0005	REM	0.54
Staging
I/II < 70%[18,20,38,42,48,49]	6	1.26 (1.09-1.45)	87	< 0.0001	REM	-
I/II ≥ 70%[15,22,26,43]	4	1.32 (1.03-1.69)	11	0.34	REM	0.69
Molecular typing
TNBC[17,19]	2	1.18 (1.01-1.38)	0	0.62	FEM	-
Gender
Male[12,13]	2	1.85 (1.25-2.72)	62	0.1	REM	-
Female[15,17-20,22,26,27,29-34,37-40,42,43,46,48,49,52-54]	26	1.29 (1.21-1.38)	65	< 0.00001	REM	0.08

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