Human epidermal growth factor receptor 2 in combined hepatocellular-cholangiocarcinoma: Prognostic and predictive guide for adjuvant chemotherapy

doi:10.3748/wjg.v32.i22.117417

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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

Retrospective Study

Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Gastroenterol. Jun 14, 2026; 32(22): 117417
Published online Jun 14, 2026. doi: 10.3748/wjg.v32.i22.117417

Table 1 Univariate and multivariate analyses of prognostic factors based on overall survival

Variable	Univariate		Multivariate
Variable	HR (95%CI)	P value	HR (95%CI)	P value
Sex
Male	Reference
Female	1.329 (0.757-2.333)	0.322
Age	1.018 (0.986-1.050)	0.273
HBV
Present	Reference
Absent	1.222 (0.741-2.015)	0.433
Liver cirrhosis
Present	Reference
Absent	1.115 (0.678-1.834)	0.668
ALB (g/L)	0.980 (0.922-1.042)	0.520
TBIL (μmol/L)	1.003 (0.983-1.024)	0.780
PT (sec)	1.016 (0.775-1.332)	0.909
AFP (ng/mL)
≤ 40	Reference
> 40	1.192 (0.736-1.931)	0.475
CA19-9 (U/mL)
≤ 25	Reference		Reference
> 25	1.698 (1.015-2.838)	0.044^a	1.285 (0.720-2.294)	0.396
Histological grade
High/median	Reference		Reference
Low	2.469 (1.445-4.213)	0.001^a	2.313 (1.354-3.953)	0.002^a
Satellite lesions
Present	Reference
Absent	0.923 (0.503-1.694)	0.795
Microvascular invasion
Present	Reference		Reference
Absent	0.575 (0.290-1.141)	0.114^a	0.734 (0.326-1.655)	0.456
Macrovascular invasion
Present	Reference		Reference
Absent	0.513 (0.302-0.872)	0.014^a	0.586 (0.343-1.000)	0.050
Lymphatic node metastasis
Present	Reference		Reference
Absent	0.566 (0.279-1.148)	0.115	0.733 (0.321-1.670)	0.459
Maximum tumor diameter (cm)
≤ 5	Reference		Reference
> 5	1.684 (1.035-2.740)	0.036^a	1.159 (0.671-2.003)	0.596
HER2
Negative	Reference		Reference
Positive	0.482 (0.281-0.826)	0.008^a	0.551 (0.318-0.953)	0.033^a
TLS score
3	Reference		Reference
2	2.910 (1.036-8.170)	0.043^a	2.069 (0.695-6.160)	0.192
1	4.400 (1.542-12.550)	0.006^a	2.331 (0.675-8.048)	0.181
0	4.569 (1.763-11.841)	0.002^a	2.461 (0.820-7.391)	0.108

^aP < 0.05.

HR: Hazard ratio; CI: Confidence interval; CA19-9: Carbohydrate antigen 19-9; HER2: Human epidermal growth factor receptor 2; HBV: Hepatitis B virus; ALB: Albumin; TBIL: Total bilirubin; PT: Prothrombin time; AFP: Alpha-fetoprotein; TLS: Tertiary lymphoid structures.

Full Size Table

Table 2 Clinicopathological characteristics of patients in the human epidermal growth factor receptor 2 positive group after propensity score matching

Characteristic	Median (IQR) or n (%)		P value
Characteristic	Chemotherapy group (n = 7)	Non-chemotherapy group (n = 14)	P value
Sex			0.533
Male	7 (100.0)	12 (85.7)
Female	0	2 (14.3)
Age	57 (54-65)	56.5 (53.8-61.5)	0.793
HBV			0.870
Present	4 (57.1)	10 (71.4)
Absent	3 (42.9)	4 (28.6)
Liver cirrhosis			0.640
Present	4 (57.1)	5 (35.7)
Absent	3 (42.9)	9 (64.3)
ALB (g/L)	41.1 (38.1-43.1)	42.4 (39.5-45.8)	0.232
TBIL (μmol/L)	22.9 (13.5-24.8)	17.7 (13.6-21.1)	0.117
PT (sec)	11.2 (10.6-11.9)	11.2 (10.7-12.3)	0.911
AFP (ng/mL)			0.877
> 40	4 (57.1)	6 (42.9)
≤ 40	3 (42.9)	8 (57.1)
Satellite lesions			1.000
Present	1 (14.3)	2 (14.3)
Absent	6 (85.7)	12 (85.7)
Microvascular invasion
Present	0	0
Absent	7 (100.0)	14 (100.0)
Macrovascular invasion			0.844
Present	2 (28.6)	2 (14.3)
Absent	5 (71.4)	12 (85.7)
Lymphatic node metastasis			0.100
Present	2 (28.6)	0
Absent	5 (71.4)	14 (100.0)
Maximum tumor diameter (cm)			1.000
≤ 5	3 (42.9)	7 (50.0)
> 5	4 (57.1)	7 (50.0)
CA19-9 (U/mL)			1.000
≤ 25	3 (42.9)	7 (50.0)
> 25	4 (57.1)	7 (50.0)
Histological grade			1.000
High/median	4 (57.1)	8 (57.1)
Low	3 (42.9)	6 (42.9)
TLS score			0.782
3	2 (28.6)	3 (21.4)
2	2 (28.6)	5 (35.7)
1	2 (28.6)	2 (14.3)
0	1 (14.3)	4 (28.6)

IQR: Interquartile ranges; CA19-9: Carbohydrate antigen 19-9; HBV: Hepatitis B virus; ALB: Albumin; TBIL: Total bilirubin; PT: Prothrombin time; AFP: Alpha-fetoprotein; TLS: Tertiary lymphoid structures.

Full Size Table

Table 3 Clinicopathological characteristics of patients in the human epidermal growth factor receptor 2 negative group after propensity score matching

Characteristic	Median (IQR) or n (%)		P value
Characteristic	Chemotherapy group (n = 13)	Non-chemotherapy group (n = 26)	P value
Sex			0.713
Male	8 (61.5)	19 (73.1)
Female	5 (38.5)	7 (26.9)
Age	52.0 (47.0-63.5)	56.5 (51.8-62.3)	0.290
HBV			0.837
Present	9 (69.2)	15 (57.7)
Absent	4 (30.8)	11 (42.3)
Liver cirrhosis			0.378
Present	2 (15.4)	9 (34.6)
Absent	11 (84.6)	17 (65.4)
ALB (g/L)	45.6 (39.6-48.6)	42.3 (39.2-44.6)	0.104
TBIL (μmol/L)	17.7 (12.9-20.6)	14.9 (12.1-21.3)	0.870
PT (seconds)	10.7 (10.5-11.5)	11.1 (10.8-11.5)	0.241
AFP (ng/mL)			0.183
> 40	2 (15.4)	11 (42.3)
≤ 40	11 (84.6)	15 (57.7)
Satellite lesions			0.852
Present	2 (15.4)	2 (7.7)
Absent	11 (84.6)	24 (92.3)
Microvascular invasion			1.000
Present	1 (7.7)	2 (7.7)
Absent	12 (9.23)	24 (92.3)
Macrovascular invasion			0.883
Present	3 (23.1)	4 (15.4)
Absent	10 (76.9)	22 (84.6)
Lymphatic node metastasis			0.852
Present	2 (15.4)	2 (7.7)
Absent	11 (84.6)	24 (92.3)
Maximum tumor diameter (cm)			1.000
≤ 5	7 (53.8)	14 (53.8)
> 5	6 (46.2)	12 (46.2)
CA19-9 (U/mL)			0.254
≤ 25	9 (69.2)	13 (50.0)
> 25	4 (30.8)	13 (50.0)
Histological grade			0.904
High/median	5 (38.5)	8 (30.8)
Low	8 (61.5)	18 (69.2)
TLS score			0.234
3	2 (15.4)	3 (11.5)
2	1 (7.7)	4 (15.4)
1	0	4 (15.4)
0	10 (76.9)	15 (57.7)

Full Size Table

Citation: Han RY, Wei YK, Liu WN, Wang YM, Song TQ, Tian XD, Xia YR, Chen L, Gong WC. Human epidermal growth factor receptor 2 in combined hepatocellular-cholangiocarcinoma: Prognostic and predictive guide for adjuvant chemotherapy. World J Gastroenterol 2026; 32(22): 117417
URL: https://www.wjgnet.com/1007-9327/full/v32/i22/117417.htm
DOI: https://dx.doi.org/10.3748/wjg.v32.i22.117417

Han RY, Wei YK, Liu WN, Wang YM, Song TQ, Tian XD, Xia YR, Chen L, Gong WC. Human epidermal growth factor receptor 2 in combined hepatocellular-cholangiocarcinoma: Prognostic and predictive guide for adjuvant chemotherapy. World J Gastroenterol 2026; 32(22): 117417 [DOI: 10.3748/wjg.v32.i22.117417]

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