KIF15、EGFR与HER2在胆囊癌中的表达及临床意义

doi:10.16139/j.1007-9610.2025.05.06

摘要/Abstract

摘要：

目的： 探讨驱动蛋白家族成员15（KIF15）、表皮生长因子受体（EGFR）与人表皮生长因子受体2（HER2）在胆囊癌（GBC）中表达及其临床与病理意义。方法： 通过免疫组织化学染色方法检测GBC组织芯片中KIF15、EGFR与HER2蛋白表达，分析其表达水平与GBC病人临床病理特征的相关性。结果： GBC KIF15、EGFR与HER2蛋白阳性表达率分别为71.6%、62.2%和51.4%，癌旁组织分别为16.7%、0和0（均P=0.000）。GBC组织中KIF15蛋白表达与肿瘤分化程度相关（P=0.006），EGFR蛋白表达与淋巴结转移与否(P=0.026)、淋巴结转移数目(P=0.012)相关，HER2蛋白表达与肿瘤分化程度(P=0.018)、肿瘤大小(P=0.005)、T分期(P=0.032)相关。KIF15与HER2共阳性GBC病人总生存均显著低于阴性者。HER2阳性表达、淋巴结转移、淋巴结转移数目是影响GBC病人总生存的独立危险因素。结论： 胆囊癌组织中KIF15、EGFR与HER2蛋白阳性表达，与GBC临床指标及不良预后相关，可能成为预测GBC预后及治疗疗效的潜在指标。

关键词: 胆囊癌, 驱动蛋白家族成员15, 表皮生长因子受体, 人表皮生长因子受体2, 临床病理特征, 预后

Abstract:

Objective To investigate the expression of kinesin family member 15(KIF15), epidermal growth factor receptor(EGFR), and human epidermal growth factor receptor 2(HER2) in gallbladder cancer(GBC) and their clinical and pathological significance. Methods Immunohistochemical staining was employed to detect the expression of KIF15, EGFR, and HER2 proteins in GBC tissue microarrays. The correlation between protein expression levels and various clinical and pathological characteristics of GBC patients was analyzed. Results The positive expression rates of KIF15, EGFR, and HER2 proteins in GBC tissues were 71.6%, 62.2%, and 51.4% respectively, compared to 16.7%, 0, and 0 in para-carcinoma tissues (all P=0.000). KIF15 expression was correlated with cancer differentiation grade (P=0.006), while EGFR expression was associated with lymph node metastasis(P=0.026) and the number of metastatic lymph nodes(P=0.012). HER2 expression was correlated with cancer differentiation grade(P=0.018), tumor size(P=0.005), and T stage(P=0.032). GBC patients with co-positive expression of KIF15 and HER2 had significantly lower overall survival compared to those with negative expression. Positive HER2 expression, lymph node metastasis, and the number of metastatic lymph nodes were identified as independent risk factors for overall survival in GBC patients. Conclusions Positive expression of KIF15, EGFR, and HER2 in GBC tissues are correlated with various clinical indicators and poorer prognosis. These proteins may serve as potential factors for predicting prognosis and evaluating therapeutic efficacy in GBC.

Key words: Gallbladder cancer (GBC), Kinesin family member 15(KIF15), Epidermal growth factor receptor(EGFR), Human epidermal growth factor receptor 2(HER2), Clinical and pathological characteristics, Prognosis

中图分类号:

R735.8

王军, 王路兵, 胡刚峰, 章波, 黄侠, 黄磊. KIF15、EGFR与HER2在胆囊癌中的表达及临床意义[J]. 外科理论与实践, 2025, 30(05): 409-416.

WANG Jun, WANG Lubing, HU Gangfeng, ZHANG Bo, HUANG Xia, HUANG Lei. Expression and clinical significance of KIF15, EGFR, and HER2 in gallbladder cancer[J]. Journal of Surgery Concepts & Practice, 2025, 30(05): 409-416.

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Spearman's correlation	KIF15	EGFR	HER2
KIF15	1 (P=0.000)	0.189 (P=0.107)	0.347 (P=0.002)
EGFR	0.189 (P=0.107)	1 (P=0.000)	0.3 (P=0.009)
HER2	0.347 (P=0.002)	0.3 (P=0.009)	1 (P=0.000)

Variable	COX coefficient	Standard deviation	Wald value	HR	P value
KIF15 positive	-0.449	0.696	0.415	0.638	0.519
EGFR positive	0.37	0.874	0.179	1.447	0.672
HER2 positive	2.192	0.703	9.713	8.956	0.002
Age	0.105	0.511	0.043	1.111	0.836
Gender-male	0.235	0.511	0.212	1.265	0.645
Differentiation grade	0.049	0.553	0.008	1.05	0.93
Tumor infiltrate	0.016	1.509	0	1.017	0.991
Lymph node metastasis	-3.346	1.474	5.155	0.035	0.023
Distant metastasis	0.163	1.771	0.008	1.177	0.927
Tumor size	-0.01	0.189	0.003	0.99	0.959
Number of metastatic lymph nodes	5.266	2.148	6.009	193.661	0.014
TNM classification	0.871	1.508	0.333	2.389	0.564
Adenosquamous carcinoma	-1.401	0.854	2.687	0.246	0.101
Squamous cell carcinoma	1.489	1.271	1.372	4.433	0.242