山东大学耳鼻喉眼学报 ›› 2025, Vol. 39 ›› Issue (4): 26-30.doi: 10.6040/j.issn.1673-3770.0.2024.367

• 临床研究 • 上一篇    下一篇

鼻咽癌组织中EphB2表达及与临床病理特征的相关性

黄巧,任毅,侯涛,廖行伟,朱子昂,詹晓琳,刘盈,尹时华   

  1. 广西医科大学第二附属医院 耳鼻咽喉头颈外科, 广西 南宁 530007
  • 出版日期:2025-07-20 发布日期:2025-08-11
  • 通讯作者: 尹时华. E-mail:shihuayin@126.com
  • 基金资助:
    国家自然科学基金(82160213,U22A2022);广西医科大学青年科学基金资助项目(GXMUYSF202345)

Expression of EphB2 in nasopharyngeal carcinoma tissues and its correlation with clinicopathological characteristics

HUANG Qiao, REN Yi, HOU Tao, LIAO Xingwei, ZHU Zi’ang, ZHAN Xiaolin, LIU Ying, YIN Shihua   

  1. Department of Otorhinolaryngology & Head and Neck Surgery, the Second Affiliated Hospital of Guangxi Medical University, Nanning 530007, Guangxi, China
  • Online:2025-07-20 Published:2025-08-11

摘要: 目的 探讨促红素人肝细胞B2(erythropoietin-producing human hepatocellular B2, EphB2)在鼻咽癌(nasopharyngeal carcinoma, NPC)患者组织中的表达及临床意义。 方法 选取194例NPC患者为研究组,80例鼻咽黏膜慢性炎患者为对照组。采用免疫组化及蛋白印迹实验检测组织中EphB2水平,Kaplan-Meier生存分析EphB2表达与NPC患者预后的关系,Cox回归分析预后不良的独立影响因素。 结果 免疫组化及蛋白印迹实验结果显示,与鼻咽黏膜慢性炎组织相比,EphB2蛋白水平在NPC组织中高表达(t=157, P<0.001)。EphB2在NPC组织中表达水平与临床分期(χ2=24.573,P<0.001)、肿瘤浸润深度2=6.280,P=0.012)、有无颈部淋巴结转移2=5.576,P=0.018)、有无远处转移2=7.588,P=0.006)、EB病毒感染(χ2=6.754,P=0.009)、是否复发2=9.182,P=0.002)有关。Kaplan-Meier曲线显示EphB2高表达的NPC患者预后不良(χ2=7.010, P=0.008)。Cox回归模型进一步发现,EphB2是影响NPC预后的独立危险因素。 结论 EphB2是影响NPC预后的独立危险因素,可能参与了NPC发生、发展过程,其有望成为NPC早期诊断及预后评估的生物学标志物及潜在治疗靶点。

关键词: 鼻咽癌, 促红素人肝细胞B2, 临床病理, 免疫组化, Cox回归分析

Abstract: Objective To investigate the expression and clinical significance of erythropoietin-producing human hepatocellular B2(EphB2)in tissues of patients with nasopharyngeal carcinoma(NPC). Methods 194 NPC patients were enrolled as the study group, and 80 patients with chronic nasopharyngeal mucosal inflammation were included as the control group. Immunohistochemistry(IHC)and Western blot were used to detect the EphB2 levels in tissues. Kaplan-Meier survival analysis was performed to evaluate the relationship between the expression of EphB2 and the prognosis of patients with NPC, and Cox regression analysis was used to identify independent risk factors for poor prognosis. Results Immunohistochemistry and protein blotting experiments showed that EphB2 protein level was highly expressed in NPC tissues compared with chronic inflammatory tissues of nasopharyngeal mucosa(t=157, P<0.001). The expression level of EphB2 in NPC tissues was correlated with clinical stage(χ2=24.573, P<0.001), depth of tumor invasion(χ2=6.280, P=0.012), presence of cervical lymph node metastasis(χ2=5.576, P=0.018), distant metastasis(χ2=7.588, P=0.006), EBV infection(χ2=6.754, P=0.009), and the presence of recurrence(χ2=9.182, P=0.002). Kaplan-Meier curves revealed that NPC patients with high EphB2 expression had a poor prognosis(χ2=7.010, P=0.008). Cox regression analysis further revealed that EphB2 was an independent risk factor affecting the prognosis of NPC. Conclusion EphB2 is an independent risk factor affecting the prognosis of NPC, which may be involved in the process of NPC occurrence and development, and it is expected to be a biological marker and potential therapeutic target for the early diagnosis and prognosis evaluation of NPC.

Key words: Nasopharyngeal carcinoma, Erythropoietin-producing human hepatocellular B2, Clinical pathology, Immunohistochemistry, Cox regression analysis

中图分类号: 

  • R739.6
[1] Chen YP, Chan ATC, Le QT, et al. Nasopharyngeal carcinoma[J]. Lancet, 2019, 394(10192): 64-80. doi:10.1016/S0140-6736(19)30956-0
[2] Wang FQ, Zhang HZ, Cheng ZG. EPHA2 promotes the invasion and migration of human tongue squamous cell carcinoma cal-27 cells by enhancing AKT/mTOR signaling pathway[J]. Biomed Res Int, 2021, 2021: 4219690. doi:10.1155/2021/4219690
[3] Husain A, Chiu YT, Sze KM, et al. Ephrin-A3/EphA2 axis regulates cellular metabolic plasticity to enhance cancer stemness in hypoxic hepatocellular carcinoma[J]. J Hepatol, 2022, 77(2): 383-396. doi:10.1016/j.jhep.2022.02.018
[4] Xiao T, Xiao YH, Wang WX, et al. Targeting EphA2 in cancer[J]. J Hematol Oncol, 2020, 13(1): 114. doi:10.1186/s13045-020-00944-9
[5] Pasquale EB. Eph receptors and ephrins in cancer progression[J]. Nat Rev Cancer, 2024, 24(1): 5-27. doi:10.1038/s41568-023-00634-x
[6] 黄巧, 尹时华. Eph/ephrin信号通路在耳鼻咽喉头颈疾病中的研究进展[J]. 中华耳科学杂志, 2024, 22(3): 504-508. doi:10.3969/j.issn.1672-2922.2024.03.031 HUANG Qiao, YIN Shihua. Progress of Research on Eph/ephrin signaling pathway in otolaryngological diseases[J]. Chinese Journal of Otology, 2024, 22(3): 504-508. doi:10.3969/j.issn.1672-2922.2024.03.031
[7] Wang FH, Zhang XT, Li YF, et al. The Chinese society of clinical oncology(CSCO): clinical guidelines for the diagnosis and treatment of gastric cancer, 2021[J]. Cancer Commun(Lond), 2021, 41(8): 747-795. doi:10.1002/cac2.12193
[8] 王靖淞, 余灿, 张西, 等. KRT4在喉癌及癌旁正常黏膜组织中的表达及临床意义[J]. 山东大学耳鼻喉眼学报, 2024, 38(3): 12-17. doi: 10.6040/j.issn.1673-3770.0.2023.097 WANG Jingsong, YU Can, ZHANG Xi, et al. Expression and clinical significance of KRT4 in laryngeal carcinoma and adjacent normal mucosal tissues[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2024, 38(3): 12-17. doi: 10.6040/j.issn.1673-3770.0.2023.097
[9] Ling JJ, Chang AS, Zhao HY, et al. EPHB2 as a recurrence-related gene and a prognostic indicator in nasopharyngeal carcinoma: a bioinformatics screening and immunohistochemistry verification[J]. Histol Histopathol, 2022, 37(9): 889-897. doi:10.14670/HH-18-459
[10] Liu W, Yu CP, Li JF, et al. The roles of EphB2 in cancer[J]. Front Cell Dev Biol, 2022, 10: 788587. doi:10.3389/fcell.2022.788587
[11] Li Y, Zhang XF. Therapeutic effects of ephrin B receptor 2 inhibitors screened by molecular docking on cutaneous squamous cell carcinoma[J]. J Dermatolog Treat, 2022, 33(1): 373-379. doi:10.1080/09546634.2020.1756201
[12] 李艳. EphB2小分子抑制剂的筛选及其抗皮肤鳞状细胞癌的研究[D]. 兰州: 兰州大学, 2022
[13] Sato S, Vasaikar S, Eskaros A, et al. EPHB2 carried on small extracellular vesicles induces tumor angiogenesis via activation of ephrin reverse signaling[J]. JCI Insight, 2019, 4(23): e132447. doi:10.1172/jci.insight.132447
[14] Bhatia S, Hirsch K, Bukkapatnam S, et al. Combined EphB2 receptor knockdown with radiation decreases cell viability and invasion in medulloblastoma[J]. Cancer Cell Int, 2017, 17: 41. doi:10.1186/s12935-017-0409-7
[15] Leung HW, Leung CON, Lau EY, et al. EPHB2 activates β-catenin to enhance cancer stem cell properties and drive sorafenib resistance in hepatocellular carcinoma[J]. Cancer Res, 2021, 81(12): 3229-3240. doi:10.1158/0008-5472.CAN-21-0184
[16] Venkitachalam S, Babu D, Ravillah D, et al. The ephrin B2 receptor tyrosine kinase is a regulator of proto-oncogene MYC and molecular programs central to barrett's neoplasia[J]. Gastroenterology, 2022, 163(5): 1228-1241. doi:10.1053/j.gastro.2022.07.045
[17] Hu YH, Xie QH, Zhao JM, et al. Interaction between the EPHB2 receptor and EFNB1 ligand drives gastric cancer invasion and metastasis via the Wnt/β-catenin/FAK pathway[J]. Int J Biol Macromol, 2024, 258(Pt 1): 128848. doi:10.1016/j.ijbiomac.2023.128848
[18] Zhou FQ, Wang BB, Wang H, et al. circMELK promotes glioblastoma multiforme cell tumorigenesis through the miR-593/EphB2 axis[J]. Mol Ther Nucleic Acids, 2021, 25: 25-36. doi:10.1016/j.omtn.2021.05.002
[19] 孙帅, 夏青, 李凡, 等. EphB2调控claudin-6对子宫内膜癌侵袭和转移的影响[J]. 临床与实验病理学杂志, 2023, 39(8): 944-952. doi:10.13315/j.cnki.cjcep.2023.08.011 SUN Shuai, XIA Qing, LI Fan, et al. EphB2 regulates the expression of claudin-6 to modulate endometrial cancer invasion and metastasis[J]. Chinese Journal of Clinical and Experimental Pathology, 2023, 39(8): 944-952. doi:10.13315/j.cnki.cjcep.2023.08.011
[1] 邱前辉,肖旭平,杨钦泰,叶菁,邓泽义,王德生,谭国林,蒋卫红,卢永田,唐隽,石照辉,邓晓聪,刘遗斌,王跃武,段传志,杜德坤,白小欣,陈文伙,莫立根,蔡楚伟,曾鹏,何旭英,杨一梅,赵洲洋,陈健龙,赵充,林志雄,李先明,李曙平,陈冬平,陈勇,黄莹,陈春燕,韩非,黄理金,瞿申红. 鼻咽癌治疗后并发颈动脉爆裂综合征的临床处理专家共识[J]. 山东大学耳鼻喉眼学报, 2025, 39(4): 1-18.
[2] 王思权,朱洪申,张晓斌,赵洲洋,马跃,杨一梅,黄理金. 放射治疗后鼻咽癌患者单侧颈内动脉栓塞术后脑卒中及颅神经麻痹的相关因素分析[J]. 山东大学耳鼻喉眼学报, 2025, 39(4): 19-25.
[3] 孙春晓,王文晴,岳田,刘济生. 高低累积顺铂剂量同步放化疗治疗鼻咽癌的疗效分析[J]. 山东大学耳鼻喉眼学报, 2025, 39(4): 31-41.
[4] 徐飞,朱光熹,王可心. 基于决策树算法构建鼻咽癌患者放疗后发生放射性口腔黏膜炎风险的预测模型[J]. 山东大学耳鼻喉眼学报, 2025, 39(4): 42-48.
[5] 王再兴,唐志元,李定波,石照辉,曾宪海,张秋航. 鼻咽癌放疗后肿瘤复发及颅底骨坏死引起颈内动脉破裂的治疗方案[J]. 山东大学耳鼻喉眼学报, 2025, 39(4): 49-58.
[6] 孙芳,谢楚波,邱前辉. 营养指标对鼻咽癌放射性颅底坏死患者创面修复影响的回顾性分析[J]. 山东大学耳鼻喉眼学报, 2025, 39(4): 59-68.
[7] 朱瑞楷,吴家荣,孙芳,谢楚波,邱前辉. 基于计算机断层扫描血管造影术评估鼻咽癌放疗后引起颈内动脉狭窄状况及其影响因素的研究[J]. 山东大学耳鼻喉眼学报, 2025, 39(4): 77-84.
[8] 覃德波,薛建成,杨文月,胡兵,陈涛,俞艳萍,孟庆国,孙焕吉,苗北平,卢永田. 鼻咽癌诊疗变革:生物标志物与鼻内镜手术协同推进早期治疗发展[J]. 山东大学耳鼻喉眼学报, 2025, 39(4): 85-92.
[9] 吴家荣,邱前辉. 颅底筋膜组织在早期复发性鼻咽癌内镜手术中的临床意义[J]. 山东大学耳鼻喉眼学报, 2025, 39(4): 108-113.
[10] 杨鸣,刘雪霞,张华. m6A识别蛋白IGF2BPs家族在头颈肿瘤中的研究进展[J]. 山东大学耳鼻喉眼学报, 2025, 39(3): 153-161.
[11] 吴敏,李正阳,孟杰,叶惠平. 程序性细胞死亡的分子机制和其在鼻咽癌中的作用[J]. 山东大学耳鼻喉眼学报, 2025, 39(2): 152-157.
[12] 张茂华,魏日富,朱忠寿,刘平,高尚,李慧凤. LncRNA PCAT-1对鼻咽癌细胞生物学行为及化疗敏感性的影响[J]. 山东大学耳鼻喉眼学报, 2025, 39(1): 68-76.
[13] 李桂,杨艳丽,李东海,闫秀英. 成人眼眶黄色肉芽肿病临床病理分析及文献复习[J]. 山东大学耳鼻喉眼学报, 2024, 38(5): 80-85.
[14] 张静祎,董湘依,牟亚魁,宋西成. 细胞焦亡在耳鼻咽喉科疾病中的研究进展[J]. 山东大学耳鼻喉眼学报, 2024, 38(4): 140-148.
[15] 王靖淞,余灿,张西,邓启成,谢卓良,赵锐,温蓓,刘海. KRT4在喉癌及癌旁正常黏膜组织中的表达及临床意义[J]. 山东大学耳鼻喉眼学报, 2024, 38(3): 12-17.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
[1] 曹忠良 . 颌面复合伤155例临床分析[J]. 山东大学耳鼻喉眼学报, 2006, 20(1): 89 -89 .
[2] 毕景云 . 鼻中隔矫正术后血肿的处理[J]. 山东大学耳鼻喉眼学报, 2006, 20(1): 90 -91 .
[3] 刘大昱,潘新良,雷大鹏,许风雷,张立强,栾信庸 . 梨状窝内侧壁癌的手术治疗[J]. 山东大学耳鼻喉眼学报, 2007, 21(1): 8 -11 .
[4] 楼正才 . 掌拳击伤鼓膜损伤机制及临床特点分析[J]. 山东大学耳鼻喉眼学报, 2008, 22(2): 188 -188 .
[5] 刘 艳,刘新义,王金平,李大健 . 后鼓室解剖结构测量观察及临床意义[J]. 山东大学耳鼻喉眼学报, 2008, 22(3): 218 -221 .
[6] 赵 敏,王守森,甄泽年,陈贤明,王茂鑫 . 鼻内镜联合显微镜行蝶窦及经蝶鞍区微创手术[J]. 山东大学耳鼻喉眼学报, 2008, 22(3): 244 -245 .
[7] 伦 杰,吕心红 . 鼻部脂溢性角化病1例[J]. 山东大学耳鼻喉眼学报, 2008, 22(3): 252 -252 .
[8] 李光照
. 选择性横行低位气管切开术[J]. 山东大学耳鼻喉眼学报, 2008, 22(4): 325 -326 .
[9] 于德先,张文山,皮士军,曹桂霞,李永强,马 庆,黄 健 . 中药止血愈创鼻腔填塞油纱条临床应用[J]. 山东大学耳鼻喉眼学报, 2008, 22(4): 340 -342 .
[10] 李瑞恒,王丽英,孙 煦 . 明胶海绵在改良泪囊鼻腔造口术中的应用[J]. 山东大学耳鼻喉眼学报, 2008, 22(4): 381 -382 .