论著

KIF15、EGFR与HER2在胆囊癌中的表达及临床意义

  • 王军 ,
  • 王路兵 ,
  • 胡刚峰 ,
  • 章波 ,
  • 黄侠 ,
  • 黄磊
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  • 上海健康医学院附属崇明医院肝胆外科,上海 202150
黄磊,E-mail:cn194705@aliyun.com

收稿日期: 2024-08-23

  网络出版日期: 2025-12-09

基金资助

上海健康医学院附属崇明医院院级课题(CMYY2023-02);上海健康医学院师资人才百人库产学研践习项目(2024);上海健康医学院附属崇明医院第四届优秀青年医学人才培养计划(2023);上海市崇明区“可持续发展科技创新行动计划”(CKY2023-21)

Expression and clinical significance of KIF15, EGFR, and HER2 in gallbladder cancer

  • WANG Jun ,
  • WANG Lubing ,
  • HU Gangfeng ,
  • ZHANG Bo ,
  • HUANG Xia ,
  • HUANG Lei
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  • Department of Hepatobiliary Surgery, Chongming Hospital Affiliated to Shanghai University of Medicine and Health Sciences, Shanghai 202150, China

Received date: 2024-08-23

  Online published: 2025-12-09

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。

本文引用格式

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 . DOI: 10.16139/j.1007-9610.2025.05.06

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.

参考文献

[1] ROA J C, GARCIA P, KAPOOR V K, et al. Gallbladder cancer[J]. Nat Rev Dis Primers, 2022, 8(1):69.
[2] 刘世博, 王许安, 刘颖斌. 胆囊癌综合治疗的研究进展[J]. 外科理论与实践, 2016, 21(4):365-368.
  LIU S B, WANG X A, LIU Y B. Recent advances in the manegement of gallbladder carcinoma[J]. J Surg Concepts Pract, 2016, 21(4):365-368.
[3] 王军, 戴文超, 雷钧, 等. 表皮生长因子受体和表皮生长因子受体Ⅲ型突变体在胆囊癌中的表达及意义[J]. 广东医学, 2016, 37(15):2304-2307.
  WANG J, DAI W C, LEI J. Expression and significance of epidermal growth factor receptor and epidermal growth factor receptor type Ⅲ mutant in gallbladder carcinoma[J]. Guangdong Med J, 2016, 37(15):2304-2307.
[4] JIN W. ErBb family proteins in cholangiocarcinoma and clinical implications[J]. J Clin Med, 2020, 9(7):2255.
[5] 张红晨, 张勇, 刘颖斌, 等. EGFR信号通路与胆囊癌靶向治疗[J]. 外科理论与实践, 2015(2):172-175.
  ZHANG H C, ZHANG Y, LIU Y B. EGFR signal pathway and gallbladder cancer target therapy[J]. J Surg Concepts Pract, 2015(2):172-175.
[6] YANG J, LIU L, XU X, et al. KIF15 promotes the deve-lopment and progression of chordoma via activating PI3K-AKT signalling pathway[J]. Heliyon, 2024, 10(8):e29386.
[7] 蔡晨. 胆囊癌辅助治疗的研究进展[J]. 外科理论与实践, 2021, 26(2):167-170.
  CAI C. Study on gallbladder cancer adjuvant therapy[J]. J Surg Concepts Pract, 2021, 26(2):167-170.
[8] 程石, 赵修浩. 胆囊癌治疗的若干热点问题[J]. 外科理论与实践, 2019, 24(2):100-104.
  CHENG S, ZHAO X H. Several hot topics on treatment of gallbladder cancer[J]. J Surg Concepts Pract, 2019, 24(2):100-104.
[9] KIM Y, JEE S, KIM H, et al. EGFR, HER2, and MET gene amplification and protein expression profiles in biliary tract cancer and their prognostic significance[J]. Oncologist, 2024, 29(8):e1051-e1060.
[10] SHUKLA P, MISHRA K, SHUKLA R, et al. Clinicopathological and prognostic significance of VEGF, PDGF-B, and HER2/neu expression in gallbladder cancer[J]. J Cancer Res Ther, 2024, 20(1):349-357.
[11] VIKASH, KAILASHIYA V, KUMAR M, et al. EGFR expression in gallbladder carcinoma in north Indian population[J]. Gulf J Oncolog, 2023, 1(42):47-52.
[12] VERMA P, GUPTA P, GUPTA N, et al. HER2/ERBB2 overexpression in advanced gallbladder carcinoma: comprehensive evaluation by immunocytochemistry and fluorescence in situ hybridisation on fine-needle aspiration cytology samples[J]. J Clin Pathol, 2024, 77(9):614-621.
[13] LI M, ZHANG Z, LI X, et al. Whole-exome and targeted gene sequencing of gallbladder carcinoma identifies recurrent mutations in the ErbB pathway[J]. Nat Genet, 2014, 46(8):872-876.
[14] DE BITTER T J J, DE REUVER P R, DE SAVORNIN LOHMAN E A J, et al. Comprehensive clinicopathological and genomic profiling of gallbladder cancer reveals actionable targets in half of patients[J]. NPJ Precis Oncol, 2022, 6(1):83.
[15] HARDING J J, PIHA-PAUL S A, SHAH R H, et al. Antitumour activity of neratinib in patients with HER2-mutant advanced biliary tract cancers[J]. Nat Commun, 2023, 14(1):630.
[16] KWON C H, SEO H I, KIM D U, et al. HER2 status based on breast cancer guidelines as a useful prognostic marker of T2 gallbladder cancer[J]. Eur J Surg Oncol, 2023, 49(2):392-398.
[17] LAPELUSA M, HEUMANN T, GOFF L, et al. Targeted therapies in advanced biliary tract cancers-a narrative review[J]. Chin Clin Oncol, 2023, 12(2):14.
[18] MISHRA S, KUMARI S, SRIVASTAVA P, et al. Genomic profiling of gallbladder carcinoma: targetable mutations and pathways involved[J]. Pathol Res Pract, 2022,232:153806.
[19] LEE C K, CHON H J, CHEON J, et al. Trastuzumab plus FOLFOX for HER2-positive biliary tract cancer refractory to gemcitabine and cisplatin: a multi-institutional phase 2 trial of the Korean cancer study group (KCSG-HB19-14)[J]. Lancet Gastroenterol Hepatol, 2023, 8(1):56-65.
[20] YANG M, ZHAO Y, LI Y, et al. Afatinib in combination with GEMOX chemotherapy as the adjuvant treatment in patients with ErbB pathway mutated, resectable gallbladder cancer: study protocol for a ctDNA-based, multicentre, open-label, randomised, controlled, phase Ⅱ trial[J]. BMJ Open, 2023, 13(2):e61892.
[21] WEI D, RUI B, QINGQUAN F, et al. KIF11 promotes cell proliferation via ERBB2/PI3K/AKT signaling pathway in gallbladder cancer[J]. Int J Biol Sci, 2021, 17(2):514-526.
[22] LI M, LIU F, ZHANG F, et al. Genomic ERBB2/ERBB3 mutations promote PD-L1-mediated immune escape in gallbladder cancer: a whole-exome sequencing analysis[J]. Gut, 2019, 68(6):1024-1033.
[23] WANG J, WANG D, FEI Z, et al. KIF15 knockdown suppresses gallbladder cancer development[J]. Eur J Cell Biol, 2021, 100(7-8):151182.
[24] GAO L, ZHAO R, LIU J, et al. KIF15 promotes progression of castration resistant prostate cancer by activating EGFR signaling pathway[J]. Front Oncol, 2021,11:679173.
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