Association of HER2 status with prognosis in gastric cancer patients undergoing R0 resection: A large-scale multicenter study in China

Table 1 Baseline and clinicopathological characteristics among gastric cancer patients with different human epidermal growth receptor 2 status n (%)

Characteristic	HER2 status		Total	χ2	P value1
	Negative (-) n = 1014	Positive (+) n = 548
Age
Median (range)	60 (21-82)	60 (20-84)	59 (20-84)
< 60 yr	504 (63.72)	287 (36.28)	791 (50.64)	1.012	0.314
≥ 60 yr	510 (66.15)	261 (33.85)	771 (49.36)
Gender				8.288	0.004
Female	274 (70.98)	112 (29.02)	386 (24.71)
Male	740 (62.93)	436 (37.07)	1176 (75.29)
Minority				11.518	< 0.001
Han population	989 (65.71)	516 (34.29)	1505 (96.35)
Others	25 (43.86)	32 (56.14)	57 (3.65)
History of familial cancer				0.144	0.705
No	890 (76.99)	266 (23.01)	1156 (88.64)
Yes	123 (78.34)	34 (21.66)	157 (11.96)
Tumor location				10.357	0.001
Non-cardia	624 (62.03)	382 (37.97)	1006 (64.40)
Cardia	390 (70.14)	166 (29.86)	556 (35.60)
Histological grade				37.822	< 0.001
High differentiation	31 (40.79)	45 (59.21)	76 (4.87)
Moderate differentiation	203 (61.89)	125 (38.11)	328 (21.00)
Low differentiation or	762 (68.40)	352 (31.60)	1114 (71.32)
Signet-ring cell cancer
Early and unreported	18 (40.91)	26 (59.09)	44 (2.82)
TNM stage				21.640	< 0.001
I	207 (55.20)	168 (44.80)	375 (24.01)
II	215 (65.55)	113 (34.45)	328 (21.00)
III	592 (68.92)	267 (31.08)	859 (54.99)
Tumor embolus				0.034	0.954
No	761 (64.88)	412 (35.12)	1173 (75.10)
Yes	253 (65.04)	136 (34.96)	389 (24.90)
Neural invasion				3.054	0.081
No	877 (65.79)	456 (34.21)	1333 (85.34)
Yes	137 (59.83)	92 (40.17)	229 (14.66)
Adjuvant chemotherapy				2.872	0.090
No	423 (62.57)	253 (37.43)	676 (43.28)
Yes	591 (66.70)	295 (33.30)	886 (56.72)
Adjuvant radiotherapy				6.396	0.011
No	936 (64.11)	524 (35.89)	1460 (93.47)
Yes	78 (76.47)	24 (23.53)	102 (6.53)

¹The parametric P value is calculated by t-test for numerical covariates and χ² test for categorical covariates. Number of observations in the original data set = 1562. Number of observations used = 1313, owing to the missing value occurring in family history of cancer (249). HER2: Human epidermal growth receptor 2.

Table 2 Hazard ratios and 95% confidence intervals for the association between potential prognosis factors and gastric cancer

Characteristic	n	DFS				OS
		HR (95%CI)1	P value1	HR (95%CI)2	P value2	HR (95%CI)1	P value1	HR (95%CI)2	P value2
Age			< 0.001		< 0.001		< 0.001		< 0.001
< 60 yr	792	1		1		1		1
≥ 60 yr	772	1.58 (1.35-1.85)		1.42 (1.18-1.71)		1.60 (1.35-1.89)		1.39 (1.15-1.70)
Gender			0.674		0.992		0.976		0.651
Female	387	1		1		1		1
Male	1177	0.96 (0.80-1.15)		1.00 (0.82-1.23)		1.00 (0.82-1.21)		1.05 (0.85-1.30)
Minority			0.364		0.600		0.563		0.797
Han population	1507	1		1		1		1
Others	57	0.81 (0.51-1.28)		0.87 (0.52-1.46)		0.87 (0.54-1.40)		0.93 (0.55-1.59)
History of familial cancer			0.367		0.295		0.610		0.523
No	1157	1		1		1		1
Yes	157	1.12 (0.87-1.44)		1.15 (0.89-1.48)		1.07 (0.82-1.41)		1.09 (0.83-1.44)
Tumor location			< 0.001		0.743		0.003		0.545
Cardia	1007	1		1		1		1
Non-cardia	557	1.34 (1.14-1.57)		0.97 (0.81-1.16)		1.29 (1.09-1.53)		0.94 (0.78-1.14)
TNM stage
I	376	1				1		1
II	329	2.71 (1.92-3.83)	< 0.001	2.61 (1.76-3.87)	< 0.001	3.27 (2.21-4.83)	< 0.001	3.33 (2.14-5.18)	< 0.001
III	859	6.25 (4.64-8.44)	< 0.001	6.50 (4.57-9.23)	< 0.001	7.58 (5.37-10.70)	< 0.001	8.70 (5.83-12.98)	< 0.001
Tumor embolus			< 0.001		0.339		< 0.001		0.802
No	1175	1		1		1		1
Yes	289	1.81 (1.53-2.13)		1.10 (0.90-1.34)		1.70 (1.43-2.03)		0.97 (0.79-1.20)
Neural invasion			< 0.001		< 0.001		< 0.001		< 0.001
No	1334	1		1		1		1
Yes	230	1.90 (1.57-2.30)		1.51 (1.21-1.89)		2.06 (1.69-2.52)		1.68 (1.33-2.12)
Adjuvant chemotherapy			0.008		0.0151		0.052		0.002
No	678	1		1		1		1
Yes	886	1.24 (1.06-1.47)		0.79 (0.65-0.95)		1.19 (1.00-1.40)		0.73 (0.60-0.90)
Adjuvant radiotherapy			0.008		0.478		0.254		0.667
No	1462	1		1		1		1
Yes	102	1.46 (1.10-1.93)		1.11 (0.83-1.49)		1.20 (0.88-1.64)		0.93 (0.67-1.29)
HER2			0.561		0.105		0.898		0.118
Negative (-)	1015	1		1		1		1
Positive (+)	549	0.95 (0.81-1.12)		1.19 (0.96-1.46)		0.99 (0.83-1.18)		1.19 (0.96-1.48)

¹HRs and 95%CI with P value based on Cox proportional hazard regression model;

²Multivariable HRs and 95%CI with P value based on Cox proportional hazard regression model. Number of observations in the original data set = 1562. Number of observations used = 1313, owing to the missing value occurring in family history of cancer (249). DFS: Disease free survival; OS: Overall survival.

Table 3 Adjusted¹ hazards ratios for the association between human epidermal growth receptor 2 status and gastric cancer stratified by age, gender, tumor location and TNM stage

Characteristic	DFS		OS
	HR (95%CI)1	Pinteraction value	HR (95%CI)1	Pinteraction value
Age		< 0.001		0.003
< 60 yr	1.00 (0.69-1.44)		1.09 (0.74-1.60)
≥ 60 yr	1.32 (1.02-1.71)		1.28 (0.98-1.68)
Gender		0.116		0.070
Female	1.10 (0.70-1.73)		1.18 (0.95-1.47)
Male	1.21 (0.96-1.53)		1.20 (0.88-1.64)
Tumor location		0.268		0.303
Non-cardia	1.22 (0.91-1.63)		1.20 (0.88-1.64)
Cardia	1.18 (0.87-1.58)		1.21 (0.88-1.65)
TNM stage		0.037		0.041
I	1.86 (0.98-3.50)		2.03 (0.97-4.23)
II	1.55 (0.94-2.55)		1.75 (1.04-2.94)
III	1.06 (0.83-1.36)		1.03 (0.79-1.33)

¹Adjusted HRs and 95%CIs are calculated using models stratified by age, gender, location and TNM stage, with additional adjustment for ethnic, history of family cancer, tumor embolus, neural invasion, adjuvant chemotherapy and adjuvant radiotherapy. Number of observations in the original data set = 1562. Number of observations used = 1313, owing to the missing value occurring in family history of cancer (249). DFS: Disease free survival; OS: Overall survival; TNM: Tumor-node-metastasis.