乳腺浸润性导管癌中survivin与NF-κB的表达及其临床意义
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杨金花, Email: jinhuay65@sina.com

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河南省科学技术厅科技攻关计划资助项目(182102311189)。


Expressions of survivin and NF-κB in invasive ductal breast cancer and their clinical significance
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    摘要:

    背景与目的:肿瘤的侵袭和转移是乳腺癌死亡的主要原因,对乳腺癌分子标记物的研究有助于诊断和预后判断,乳腺癌组织中凋亡基因survivin和核转录因子NF-κB蛋白的关系尚不清楚,本研究探讨乳腺浸润性导管癌组织中survivin和NF-κB蛋白的表达及其与患者临床病理特征、分子亚型及预后的关系,以期拓展对乳腺癌发病机制的理解与认识,为乳腺癌防治提供新策略。
    方法:选择2015年5月—2017年5月在郑州人民医院行手术治疗、术后经病理确诊且病历完整的80例乳腺浸润性导管癌患者作为研究对象,用免疫组化法检测患者癌组织与癌旁组织在survivin与NF-κB蛋白的表达,用统计学方法分析survivin、NF-κB蛋白与患者临床病理参数、分子亚型及预后的关系。
    结果:survivin与NF-κB在乳腺浸润性导管癌组织中的阳性表达率均明显高于癌旁组织(53.75% vs. 11.25%;56.25% vs. 8.75%,均P<0.05)。survivin和NF-κB的表达均与组织学分化、淋巴结转移状况、TNM分期、分子分型有关,均表现为在低分化、淋巴结转移阳性、TNM分期晚、非luminal型乳腺癌组织中高表达(均P<0.05);同时,两者共高表达率也在低分化、淋巴结转移阳性、TNM分期晚、非luminal型的乳腺癌组织明显升高(均P<0.05)。乳腺浸润性导管癌组织中survivin和NF-κB表达呈正相关(r=0.546,P=0.000)。生存分析结果显示,survivin或NF-κB高表达患者的5年无病生存率均低于各自的低表达患者,而两者共高表达的患者5年无病生存率低于两者任何单一高表达或两者共低表达患者(均P<0.05)。Cox回归分析显示,NF-κB、survivin与NF-κB共表达、肿物直径、分化程度和淋巴结转移是乳腺浸润性导管癌患者预后的独立危险因素(均P<0.05)。
    结论:乳腺浸润性导管癌组织中survivin和NF-κB蛋白的表达与患者的恶性临床病理特征及不良预后密切相关,而且两者可能存在协同作用促进了乳腺癌的发生与发展。

    Abstract:

    Background and Aims: Tumor invasion and metastasis are the main causes of death in breast cancer. The study of molecular markers of breast cancer is helpful for diagnosis and prognosis estimation. The relationship between apoptotic gene survivin and nuclear transcription factor NF-κB in breast cancer tissue is still unclear. This study was conducted to investigate the expressions of survivin and NF-κB protein in breast invasive ductal carcinoma and their relations with the clinicopathologic features, molecular subtypes and prognosis of the patients, so as to expand the understanding and knowledge of the pathogenesis for breast cancer and provide new strategies for the treatment and prevention of breast cancer.
    Methods: Eighty patients with invasive ductal breast cancer who underwent surgical treatment in the People's Hospital of Zhengzhou from May 2015 to May 2017 and had confirmed pathological diagnosis and complete clinical data were selected as study objects. The expressions of survivin and NF-κB protein in the tumor and adjacent tissues from the patients were determined by immunohistochemical staining. The relations of survivin and NF-κB protein expressions with the clinicopathologic variables and molecular subtypes as well as prognosis of the patients were analyzed by statistical methods. 
    Results: The positive expression rates of both survivin and NF-κB protein in cancer were significantly higher than those in adjacent tissue (53.75% vs. 11.25%; 56.25% vs. 8.75%, both P<0.05). Both expressions of survivin and NF-κB were associated with histological grade, lymph node status and TNM stage, and both expressions were increased in breast cancer tissue of poor differentiation, positive lymph node metastasis, advanced TNM stages and non-luminal subtypes (all P<0.05); meanwhile, the co-overexpression rates of survivin and NF-κB were higher in breast cancer tissue of poor differentiation, positive lymph node metastasis, advanced TNM stages and non-luminal subtypes (all P<0.05). There was a positive correlation between survivin and NF-κB expressions (r=0.546, P=0.000). Survival analysis showed that the 5-year disease-free survival rate of patients with either high survivin or NF-κB expression was lower than those of the patients with corresponding low expression, and the 5-year disease-free survival rate of patients with co-overexpression of survivin and NF-κB was lower than that of the patients with either high survivin or NF-κB expression alone as well as patients with co-downexpression of survivin and NF-κB (all P<0.05). Cox regression analysis showed that NF-κB, co-expression of survivin and NF-κB, tumor diameter, differentiation and lymph node metastasis were independent risk factors for the prognosis of patients with invasive ductal breast cancer (all P<0.05).
    Conclusion: The expressions of survivin and NF-κB protein in invasive ductal breast cancer tissue are closely related to the malignant clinicopathologic features and unfavorable prognosis of the patients, and furthermore, there may be a synergistic action between survivin and NF-κB in promoting the occurrence and development of breast cancer. 

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王建君, 徐小艳, 冯智坤, 杨金花.乳腺浸润性导管癌中survivin与NF-κB的表达及其临床意义[J].中国普通外科杂志,2020,29(11):1327-1335.
DOI:10.7659/j. issn.1005-6947.2020.11.006

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  • 收稿日期:2019-12-02
  • 最后修改日期:2020-05-13
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  • 在线发布日期: 2020-11-25