Prognostic value of hypoxia-inducible factor-1 alpha and prolyl 4-hydroxylase beta polypeptide overexpression in gastric cancer

doi:10.3748/wjg.v24.i22.2381

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Jun 14, 2018 (publication date) through Jan 22, 2025

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Gastroenterol. Jun 14, 2018; 24(22): 2381-2391
Published online Jun 14, 2018. doi: 10.3748/wjg.v24.i22.2381

Table 1 Patients characteristics and univariate analysis (n = 428)

Characteristics	n (%)	DFS			OS
Characteristics	n (%)	t/mo	P value	χ²/Z	t/mo	P value	χ²/Z
Age (median, yr)			0.47	-0.72		0.79	-0.26
< 60	199 (46.5)	40.02			44.97
≥ 60	229 (53.5)	37.72			44.34
Gender			0.42	-0.80		0.56	-0.59
Male	304 (71.0)	37.74			43.99
Female	124 (29.0)	41.38			46.23
Bormann type			0.00	78.58		0.00	70.97
I	33 (7.7)	64.24			64.21
II	189 (44.2)	45.99			51.15
III	200 (46.7)	28.43			35.78
IV	6 (1.4)	17.50			27.33
Tumor size			0.00	-6.17		0.00	-5.87
< 5 cm	243 (56.8)	46.15			50.57
≥ 5 cm	185 (43.2)	29.12			36.84
Location			0.09	4.92		0.22	3.03
Up	90 (21.0)	33.10			40.62
Middle	121 (28.3)	39.98			45.26
Low	217 (50.7)	40.49			45.96
Tumor histological morphology			0.26	2.70		0.36	2.03
Adenocarcinoma	319 (74.5)	39.45			45.15
Absolute signet ring cell carcinoma	3 (0.7)	63.67			63.67
Mixed carcinoma	106 (24.8)	36.09			42.56
Lauren type			0.07	5.28		0.06	5.50
Intestinal	200 (49.5)	41.74			47.59
Diffuse	129 (26.9)	39.28			44.97
Mixed type	99 (23.1)	33.96			40.12
Tumor differentiation			0.01	-2.74		0.01	-2.54
Poor	288 (67.3)	36.54			42.72
Moderate and high	140 (32.7)	43.43			48.58
Vessel invasion			0.00	-6.06		0.00	-5.65
No	299 (69.9)	43.24			48.60
Yes	129 (30.1)	28.49			35.47
Perineural invasion			0.00	-5.63		0.00	-5.26
No	320 (74.8)	42.76			47.95
Yes	108 (25.2)	27.03			34.82
T category			0.00	143.15		0.00	124.25
T1	85 (19.9)	65.15			65.20
T2	24 (5.6)	61.13			62.44
T3	16 (3.7)	59.04			61.33
T4	303 (70.8)	28.61			36.61
N category			0.00	323.31		0.00	322.11
N0	179 (41.8)	62.20			63.47
N1	67 (15.7)	37.22			48.52
N2	84 (19.6)	23.48			33.05
N3	98 (22.9)	10.24			17.52
TNM stage			0.00	285.22		0.00	271.25
I	93 (21.7)	64.16			64.20
II	101 (23.6)	63.27			65.59
III	228 (53.3)	18.44			28.30
IV	6 (1.4)	7.00			9.50
Operation			0.00	-3.45		0.00	-3.79
D1	5 (1.2)	7.00			9.20
D2	423 (98.8)	39.17			45.06
Hepatic metastasis			0.00	-5.31		0.00	-5.10
Yes	46 (10.7)	18.48			28.22
No	382 (89.3)	41.24			46.62
Peritoneum cavity metastasis			0.00	-14.35		0.00	-13.96
Yes	155 (36.2)	14.45			23.47
No	273 (63.8)	52.61			56.66
HIF-1α			0.00	-4.41		0.00	-4.24
Weak-expression	209 (48.8)	44.80			49.58
Over- expression	219 (51.2)	33.06			39.92
P4HB			0.00	-6.88		0.00	-6.91
Weak-expression	213 (49.8)	48.03			52.48
Over- expression	215 (50.2)	29.64			36.87

DFS: Disease-free survival; OS: Overall survival; HIF-1α: Hypoxia-inducible factor-1α; P4HB: Prolyl 4-hydroxylase beta.

Table 2 Hypoxia-inducible factor-1α and prolyl 4-hydroxylase beta expressions and clinicopathologic characteristics

Characteristics	HIF-1α				P4HB
Characteristics	Low	High	P value	χ²	Low	High	P value	χ²
	209 (48.8)	219 (51.2)			213 (49.8)	215 (50.2)
Age			0.42	0.65			0.35	0.57
< 60	93 (46.7)	106 (53.3)			96 (48.2)	103 (51.8)
≥ 60	116 (50.7)	113 (49.3)			117 (51.1)	112 (48.9)
Gender			0.91	0.01			0.48	0.49
Male	149 (49.0)	155 (51.0)			148 (48.7)	156 (51.3)
Female	60 (48.4)	64 (51.6)			65 (52.4)	59 (47.6)
Bormann type			0.06	7.26			0.00	29.18
I	16 (48.5)	17 (51.5)			26 (78.8)	7 (21.2)
II	104 (55.0)	85 (45.0)			110 (58.2)	79 (41.8)
III	88 (44.0)	112 (56.0)			75 (37.5)	125 (62.5)
V	1 (16.7)	5 (83.3)			2 (33.3)	4 (66.7)
Tumor size			0.30	1.09			0.00	11.09
< 5 cm	124 (51.0)	119 (49.0)			138 (42.0)	110 (58.0)
≥ 5 cm	85 (45.9)	100 (54.1)			75 (14.6)	105 (85.4)
Tumor histological morphology			0.18	3.45			0.49	1.42
Adenocarcinoma	157 (49.2)	162 (50.8)			163 (51.1)	156 (48.9)
Absolute signet ring cell carcinoma	3 (100.0)	0 (0.0)			2 (66.7)	1 (33.3)
Mixed carcinoma	49 (46.2)	57 (53.8)			48 (45.3)	58 (54.7)
Location			0.15	3.78			0.63	0.94
Up	40 (14.4)	50 (55.6)			41 (45.6)	49 (54.4)
Middle	53 (43.8)	68 (56.2)			60 (49.6)	61 (50.4)
Low	116 (53.5)	101 (46.5)			112 (51.6)	105 (48.4)
Lauren type			0.05	5.98			0.57	1.14
Intestinal	96 (48.0)	104 (52.0)			104 (52.0)	96 (48.0)
Diffuse	73 (56.6)	56 (43.4)			64 (49.6)	65 (50.4)
Mixed type	40 (40.4)	59 (59.6)			45 (45.5)	54 (54.5)
Tumor differentiation			0.08	3.17			0.03	4.53
Poor	132 (45.8)	156 (54.2)			133 (46.2)	155 (53.8)
Moderate and high	77 (55.0)	63 (45.0)			80 (57.1)	60 (42.9)
Vessel invasion			0.21	1.60			0.38	0.78
No	152 (50.8)	147 (49.2)			153 (51.2)	146 (48.8)
Yes	57 (44.2)	72 (55.8)			60 (46.5)	69 (53.5)
Perineural invasion			0.41	0.69			0.03	4.71
No	160 (50.0)	160 (50.0)			169 (52.8)	151 (47.2)
Yes	49 (45.4)	59 (54.6)			44 (40.7)	92 (59.3)
T category			0.01	10.93			0.00	44.94
T1	32 (88.9)	4 (11.1)			9 (56.3)	7 (43.8)
T2	11 (45.8)	13 (54.2)			13 (54.2)	11 (45.8)
T3	41 (45.1)	50 (54.9)			69 (81.2)	16 (18.8)
T4	125 (45.1)	152 (54.9)			122 (40.3)	181 (59.7)
N category			0.00	23.55			0.00	54.13
N0	111 (62.0)	68 (38.0)			126 (70.4)	53 (29.6)
N1	28 (41.8)	39 (58.2)			28 (41.8)	39 (58.2)
N2	37 (44.0)	47 (56.0			28 (33.3)	56 (66.7)
N3	33 (33.7)	65 (66.3)			31 (31.6)	67 (68.4)
TNM stage			0.00	23.32			0.00	65.64
I	54 (58.1)	39 (41.9)			72 (77.4)	21 (22.6)
II	65 (64.4)	36 (35.6)			65 (64.4)	36 (35.6)
III	87 (38.2)	141 (61.8)			75 (32.9)	1503 (67.1)
IV	3 (50.0)	3 (50.0)			1 (16.7)	5 (83.3)
Operation			0.69	0.16			0.18	1.79
D1	2 (40.0)	3 (60.0)			1 (20.0)	4 (80.0)
D2	207 (48.9)	216 (51.1)			212 (50.1)	211 (49.9)
Hepatic metastases			0.01	6.98			0.07	3.38
Yes	14 (30.4)	32 (69.6)			17 (37.0)	29 (63.0)
No	195 (51.0)	187 (49.0)			196 (51.3)	186 (48.7)
Peritoneum cavity metastasis			0.00	12.67			0.00	39.29
Yes	58 (37.4)	97 (62.6)			46 (29.7)	109 (70.3)
No	151 (55.3)	122 (44.7)			167 (61.2)	106 (38.8)

HIF-1α: Hypoxia-inducible factor-1α; P4HB: Prolyl 4-hydroxylase beta.

Table 3 Multivariate analysis of significant prognostic factor for survival in gastric cancer patients

Variables	DFS			OS
Variables	P value	HR	95%CI	P value	HR	95%CI
Bormann	0.26	1.15	0.91-1.46	0.38	1.11	0.88-1.40
Tumor Size	0.34	0.88	0.67-1.15	0.38	0.89	0.68-1.16
Tumor differentiation	0.95	0.99	0.74-1.33	0.84	1.03	0.77-1.31
Vessel invasion	0.01	0.70	0.53-0.93	0.19	0.83	0.63-1.09
Perineural invasion	0.44	0.90	0.68-1.19	0.25	0.86	0.66-1.11
TNM stage	0.00	24.65	16.04-37.87	0.00	87.72	41.21-186.68
HIF-1α expression	0.00	0.67	0.52-0.88	0.00	0.65	0.50-0.85
P4HB expression	0.04	0.76	0.58-1.00	0.65	0.94	0.72-1.23

DFS: Disease-free survival; OS: Overall survival; HIF-1α: Hypoxia-inducible factor-1α; P4HB: Prolyl 4-hydroxylase beta.

Citation: Zhang J, Wu Y, Lin YH, Guo S, Ning PF, Zheng ZC, Wang Y, Zhao Y. Prognostic value of hypoxia-inducible factor-1 alpha and prolyl 4-hydroxylase beta polypeptide overexpression in gastric cancer. World J Gastroenterol 2018; 24(22): 2381-2391
URL: https://www.wjgnet.com/1007-9327/full/v24/i22/2381.htm
DOI: https://dx.doi.org/10.3748/wjg.v24.i22.2381