Notch1信号通路与宫颈癌血管生成拟态的相关性

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摘要目的探究Notch1信号通路与宫颈癌血管生成拟态（VM）的相关性。方法收集2012年1月~2015年12月于湖北省中医院行手术治疗的68例宫颈癌患者的石蜡切片为宫颈癌组，另选择27例因子宫肌瘤行手术治疗患者的正常宫颈切片作对照组。CD31免疫组化法和过碘酸-雪夫氏（PAS）反应检测VM形成情况。免疫组化法检测Jagged1、Notch1和Hes1表达情况。分析VM与Jagged1、Notch1和Hes1的相关性。分析VM、Jagged1、Notch1和Hes1与患者临床病理参数和术后预后的关系。结果 Jagged1、Notch1和Hes1在宫颈癌组中的阳性表达率均显著高于对照组（P < 0.01）。VM仅存在于宫颈癌组织中，且阳性率约39.7%。Jagged1与宫颈癌淋巴结转移有关（P < 0.05）。Notch1与肿瘤大小及组织分化有关（P < 0.01）。Hes1与患者的临床病理参数均无关（P > 0.05）。VM与肿瘤大小及淋巴结转移有关（P < 0.01）。VM与Jagged1、Notch1的表达呈正相关（r = 0.283、0.304，均P < 0.05）。VM是宫颈癌术后预后的独立危险因素（HR = 2.21，95%CI：1.85~2.64，P < 0.05）。结论宫颈癌VM形成预示着患者不良的术后预后。宫颈癌组织中表达上调的Jagged1-Notch1信号通路可能参与促VM形成。未来针对Notch1通路的靶点治疗有望抗宫颈癌VM形成以及改善患者的预后。

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	方虹1 周忠明1 李云君1 鲁林2

关键词 ：宫颈癌, 血管生成拟态, Notch1信号通路, 免疫组化

Abstract：Objective To explore the correlation between Notch1 signaling pathway and vasculogenic mimicry (VM) in cervical cancer. Methods Paraffin sections were collected from 68 cervical cancer patients who underwent surgical treatment in Hubei Provincial Hospital of Traditional Chinese Medicine between January 2012 and December 2015 as cervical cancer group. Paraffin sections of normal cervix were also collected from 27 patients who were surgically treated for uterine leiomyoma as control group. CD31 immunohistochemistry and periodic acid-Schiff (PAS) reaction were performed to detect VM formation. IHC was performed to detect Jagged1, Notch1 and Hes1 expression. The correlations of VM with Jagged1, Notch1 and Hes1 were analyzed. The correlations of VM, Jagged1, Notch1 and Hes1 with patients′ clinic-pathological features and postoperative prognosis were analyzed. Results The positive expression rates of Jagged1, Notch1 and Hes1 in cervical cancer group were significantly higher than those in control group (P < 0.05). VM was only in cervical cancer tissues, with the positive expression rate of 39.7%. Jagged1 was associated with lymph node metastasis of cervical cancer (P < 0.05). Notch1 was associated with tumor size and tissue differentiation (P < 0.01). Hes1 was not associated with any clinic-pathological parameters of patients (P > 0.05). VM was associated with tumor size and lymph node metastasis (P < 0.01). VM was positively correlated with Jagged1 and Notch1 expression (r = 0.283, 0.304, all P < 0.05). VM was an independent risk factor for postoperative prognosis of cervical cancer patients (HR = 2.21, 95%CI: 1.85-2.64, P < 0.05). Conclusion VM formation in cervical cancer predicts patients′ poor postoperative prognosis. The up-regulated Jagged1/Notch1 signaling pathway in cervical cancer might be involved in promoting VM formation. In the future, targeted Notch1 pathway treatment might be expected to prevent VM formation in cervical cancer and improve patients′ prognosis.

Key words： Cervical cancer Vasculogenic mimicry Notch1 signaling pathway Immunohistochemistry

基金资助:湖北省高校人文社会科学重点研究基地中医药发展研究中心年度重点项目和一般项目（ZX2015D06）。

通讯作者: 鲁林（1981-），男，硕士；研究方向：肿瘤血道转移、骨转移的机制。

作者简介: 方虹（1983-），女，硕士；研究方向：妇科常见肿瘤的诊治。

引用本文:

方虹1 周忠明1 李云君1 鲁林2. Notch1信号通路与宫颈癌血管生成拟态的相关性[J]. 中国医药导报, 2019, 16(21): 88-92.
FANG Hong1 ZHOU Zhongming1 LI Yunjun1 LU Lin2. The correlation between Notch1 signaling pathway and vasculogenic mimicry in cervical cancer. 中国医药导报, 2019, 16(21): 88-92.

链接本文:

http://www.yiyaodaobao.com.cn/CN/ 或 http://www.yiyaodaobao.com.cn/CN/Y2019/V16/I21/88

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