切换至 "中华医学电子期刊资源库"
高级检索
中华乳腺病杂志(电子版)

中华乳腺病杂志(电子版) ›› 2019, Vol. 13 ›› Issue (06) : 331 -335. doi: 10.3877/cma.j.issn.1674-0807.2019.06.003

所属专题： 文献；

论著

Delta/Notch样表皮生长因子相关受体在三阴性乳腺癌中的表达及临床意义
黄红梅1, 荣欣欣1, 李静佳1, 谢少利2, 杨懿1, 周方方1, 李金穗2, 侯令密2, 邓世山1, 刘家有1,†()   
  1. 1. 637000　四川　南充，川北医学院人体解剖学教研室
    2. 637000　四川　南充，川北医学院附属医院甲状腺乳腺外科
  • 收稿日期:2019-05-04 出版日期:2019-12-01
  • 通信作者: 刘家有
  • 基金资助:
    四川省教育厅创新团队资助项目(17TD0016); 川北医学院科研发展计划资助项目(CBY15-A-ZD17；CBY17-A-ZD08); 南充市科技与知识产权局市校科技战略合作专项(NSMC20170401)

Expression of Delta/Notch-like epidermal growth factor-related receptor in triple negative breast cancer and its clinical significance

Hongmei Huang1, Xinxin Rong1, Jingjia Li1, Shaoli Xie2, Yi Yang1, Fangfang Zhou1, Jinsui Li2, Lingmi Hou2, Shishan Deng1, Jiayou Liu1,†()   

  1. 1. Department of Anatomy, North Sichuan Medical College, Nanchong 637000, Sichuang Province, China
    2. Department of Thyroid and Breast Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuang Province, China
  • Received:2019-05-04 Published:2019-12-01
  • Corresponding author: Jiayou Liu
  • About author:
    Corresponding author: Liu Jiayou, Email:
全文 ( ) 下载PDF ( ) 导出引用
引用本文：

黄红梅, 荣欣欣, 李静佳, 谢少利, 杨懿, 周方方, 李金穗, 侯令密, 邓世山, 刘家有. Delta/Notch样表皮生长因子相关受体在三阴性乳腺癌中的表达及临床意义[J]. 中华乳腺病杂志(电子版), 2019, 13(06): 331-335.

Hongmei Huang, Xinxin Rong, Jingjia Li, Shaoli Xie, Yi Yang, Fangfang Zhou, Jinsui Li, Lingmi Hou, Shishan Deng, Jiayou Liu. Expression of Delta/Notch-like epidermal growth factor-related receptor in triple negative breast cancer and its clinical significance[J]. Chinese Journal of Breast Disease(Electronic Edition), 2019, 13(06): 331-335.

目的

探讨Delta/Notch样表皮生长因子相关受体(DNER)在三阴性乳腺癌(TNBC)中的表达情况，并分析其与患者的临床病理特征之间的关系。

方法

收集2017年3月至2018年3月川北医学院附属医院收治的39例TNBC患者的癌组织及癌旁正常组织标本进行回顾性研究，运用组织切片免疫组织化学法检测DNER蛋白表达水平，用RT-PCR检测组织中DNER mRNA表达水平。用配对χ2检验(McNemar检验)比较乳腺癌组织及癌旁正常组织中DNER阳性率的差异，用χ2检验或Fisher精确概率法分析DNER蛋白表达与患者临床病理特征之间的关系。用配对t检验比较DNER mRNA在乳腺癌组织与癌旁正常组织中的表达水平，用方差分析和独立样本t检验分析DNER mRNA表达与乳腺癌患者临床病理特征的关系，两两比较用LSD法。

结果

DNER蛋白在TNBC组织中的阳性表达率为82.1%(32/39)，高于在癌旁正常组织中的阳性表达率(23.1%, 9/39)(P<0.001)。DNER蛋白在TNBC组织中的阳性表达率与肿瘤直径(χ2＝ 6.121，P＝0.026)、淋巴结转移(P＝0.005)及TNM分期(P＝0.030)有关。RT-PCR检验结果显示，DNER mRNA在TNBC组织中的相对表达量高于其癌旁正常组织(0.768±0.067比0.487±0.041，t＝4.793, P<0.001)；DNER mRNA在TNBC组织中的表达与肿瘤直径、TNM分期及淋巴结转移有关(F＝8.392, P＝0.001; t＝5.178，P<0.001; t＝4.925，P<0.001)。

结论

DNER蛋白及mRNA的高表达与TNBC的发生、发展及转移密切相关，可能是乳腺癌诊断和治疗的潜在靶标。

关键词: 乳腺肿瘤, 淋巴转移, 肿瘤分期, 受体，Notch
Objective

To explore the expression of Delta/Notch-like epidermal growth factor-related receptor (DNER) in triple negative breast cancer (TNBC) and analyze its correlation with clinicopathological characteristics of TNBC patients.

Methods

The samples of cancer tissues and adjacent normal tissues were collected from 39 cases of TNBC in the Affiliated Hospital of North Sichuan Medical College from March 2017 to March 2018 for a retrospective study. The protein and mRNA expressions of DNER in samples were detected by immunohistochemistry and RT-PCR, respectively. The paired χ2 test (McNemar test) was used to compare the DNER-positive rates between breast cancer tissues and adjacent normal tissues. χ2 test or Fisher’s exact test was used to analyze the relationship between DNER protein expression and clinicopathological characteristics of TNBC patients. The DNER mRNA expression was compared between breast cancer tissues and adjacent normal tissues by paired t test. The correlation between DNER mRNA expression and clinicopathological characteristics was analyzed by independent-sample t test and analysis of variance. Pairwise comparison was performed using the LSD test.

Results

Immunohistochemical results showed that the positive rate of DNER protein in TNBC tissues was 82.1%(32/39), significantly higher than 23.1% (9/39) in adjacent normal tissues (P<0.001), and the positive rate of DNER protein was associated with tumor diameter (χ2= 6.121, P=0.026), TNM staging (P=0.030) and lymph node metastases (P=0.005). Results of RT-PCR showed that DNER mRNA expression in TNBC tissues was 0.768±0.067, significantly higher than 0.487±0.041 in adjacent normal tissues (t=4.793, P<0.001). The expression of DNER mRNA in TNBC tissues was correlated with tumor diameter (F=8.392, P=0.001), TNM staging (t=5.178, P<0.001) and lymph node metastases (t=4.925, P<0.001).

Conclusion

The high expression of DNER protein and mRNA is closely related to the occurrence, development and metastasis of TNBC, so DNER may be a potential target for the diagnosis and treatment of TNBC.

Key words: Breast neoplasms, Lymphatic metastasis, Neoplasm staging, Receptors, Notch
图1 DNER蛋白在三阴性乳腺癌组织及癌旁正常组织中的表达情况(SP ×200)　a图所示DNER蛋白在三阴性乳腺癌组织中高表达；b图所示DNER蛋白在癌旁正常组织中低表达
表1 Delta/Notch样表皮生长因子相关受体蛋白在三阴性乳腺癌组织及癌旁正常组织中的表达(例)
乳腺癌组织 癌旁正常组织 合计
阳性 阴性
阳性 9 23 32
阴性 0 7 7
合计 9 30 39
表2 39例三阴性乳腺癌患者的临床病理特征与DNER蛋白表达的关系[例(%)]
临床病理特征 例数 DNER蛋白表达 检验值 P值
阳性 阴性
年龄 ? ? ? ? ?
? ≤45岁 24 21(87.5) 3(12.5) ? 0.396a
? >45岁 15 11(73.3) 4(26.7) ? ?
肿瘤直径 ? ? ? ? ?
? ≤2 cm 12 7(58.3) 5(41.7) ? ?
? >2～5 cm 17 15(88.2) 2(11.8) χ2＝6.121 0.026a
? >5 cm 10 10(100) 0(0) ? ?
淋巴结转移 ? ? ? ? ?
? 有 26 24(92.3) 2(7.7) ? 0.030a
? 无 13 8(61.5) 5(38.5) ?
TNM分期 ? ? ? ? ?
? Ⅰ～Ⅱ期 14 8(57.1) 6(42.9) ? ?
? Ⅲ～Ⅳ期 25 24(96.0) 1(4.0) ? 0.005a
图2 部分三阴性乳腺癌患者DNER mRNA的PCR扩增产物电泳图
表3 39例三阴性乳腺癌患者的临床病理特征与DNER mRNA表达之间的关系
临床病理特征 例数 DNER mRNA表达 检验值 P值
年龄 ? ? ? ?
? ≤45岁 24 0.805±0.085 t＝0.690 0.494
? >45岁 15 0.709±0.112
肿瘤直径 ? ? ? ?
? ≤2 cm 8 0.356±0.039 ? ?
? >2～5 cm 24 0.811±0.053a F＝8.392 0.001
? >5 cm 7 1.091±0.072a ? ?
淋巴结转移 ? ? ? ?
? 有 28 0.902±0.085 t＝4.925 <0.001
? 无 11 0.426±0.069
TNM分期 ? ? ? ?
? Ⅰ～Ⅱ期 10 0.527±0.058 t＝5.178 <0.001
? Ⅲ～Ⅳ期 29 0.894±0.075
[1]
令狐锐霞，司文，李莹，等. 3846例乳腺癌流行病学及临床病理学分析[J]. 解放军医学院学报，2015，36(10):1017-1021,1038.
[2]
Fan L, Strasser-Weippl K, Li JJ, et al. Breast cancer in China[J]. Lancet Oncol, 2014，15(7):e279-e289.
[3]
Beiki O, Hall P, Ekbom A, et al. Breast cancer incidence and case fatality among 4.7 million women in relation to social and ethnic background: a population-based cohort study[J]. Breast Cancer Res, 2012，14(1):R5.
[4]
Eiraku M, Hirata Y, Takeshima H, et al. Delta/notch-like epidermal growth factor (EGF)-related receptor, a novel EGF-like repeat-containing protein targeted to dendrites of developing and adult central nervous system neurons[J]. J Biol Chem, 2002，277(28):25 400-25 407.
[5]
Sun P, Xia S, Lal B, et al. DNER, an epigenetically modulated gene, regulates glioblastoma-derived neurosphere cell differentiation and tumor propagation[J]. Stem Cells, 2009，27(7):1473-1486.
[6]
Park JR, Jung JW, Seo MS, et al. DNER modulates adipogenesis of human adipose tissue-derived mesenchymal stem cells via regulation of cell proliferation[J]. Cell Prolif, 2010，43(1):19-28.
[7]
Wang L, Wu Q, Zhu S, et al. Delta/notch-like epidermal growth factor-related receptor (DNER) orchestrates stemness and cancer progression in prostate cancer[J]. Am J Transl Res, 2017，9(11):5031-5039.
[8]
Wang L, Wu Q, Zhu S, et al. Quantum dot-based immunofluorescent imaging and quantitative detection of DNER and prognostic value in prostate cancer[J]. Cancer Biomark, 2018，22(4):683-691.
[9]
Liang Y, Luo H, Zhang H, et al. Oncogene delta/notch-like EGF-related receptor promotes cell proliferation, invasion, and migration in hepatocellular carcinoma and predicts a poor prognosis[J]. Cancer Biother Radiopharm, 2018，33(9):380-386.
[10]
刘家有，邓世山，朱剑军，等. 免疫组织化学法和qPCR技术检测FBP1在结直肠腺癌中的表达及临床意义[J]. 川北医学院学报，2017，32(2):167-171.
[11]
刘家有，熊东，王卓娜，等. Cdc37在结直肠腺癌中的表达及临床意义的研究[J]. 实用肿瘤杂志，2014，29(5):436-440.
[12]
Dadiani M, Bossel BN, Paluch-Shimon S, et al. Tumor evolution inferred by patterns of microRNA expression through the course of disease, therapy, and recurrence in breast cancer[J]. Clin Cancer Res, 2016，22(14):3651-3662.
[13]
何国德，唐孝华，于晓红，等. 动态增强磁共振成像在早期乳腺癌诊断中价值分析[J]. 川北医学院学报，2013(04):365-367.
[14]
佘青，李有怀，程永刚，等. 全腔镜乳房皮下腺体切除术联合腔镜前哨淋巴结活检术治疗早中期乳腺癌的技巧探讨[J]. 川北医学院学报，2016(05):756-758.
[15]
Keeley PW, Reese BE. DNER and NFIA are expressed by developing and mature AII amacrine cells in the mouse retina[J]. J Comp Neurol, 2018，526(3):467-479.
[16]
Chapman EJ, Williams SV, Platt FM, et al. Integrated genomic and transcriptional analysis of the in vitro evolution of telomerase-immortalized urothelial cells (TERT-NHUC)[J]. Genes Chromosomes Cancer, 2009，48(8):694-710.
[17]
Katoh M, Katoh M. Notch signaling in gastrointestinal tract (review)[J]. Int J Oncol, 2007，30(1):247-251.
[18]
Hancock DB, Soler Artigas M, Gharib SA, et al. Genome-wide joint meta-analysis of SNP and SNP-by-smoking interaction identifies novel loci for pulmonary function[J]. PLoS Genet, 2012，8(12):e1003098.
[19]
Hanson RL, Muller YL, Kobes S, et al. A genome-wide association study in American Indians implicates DNER as a susceptibility locus for type 2 diabetes[J]. Diabetes, 2014，63(1):369-376.
[1] 郏亚平, 曾书娥. 含鳞状细胞癌成分的乳腺化生性癌的超声与病理特征分析[J]. 中华医学超声杂志（电子版）, 2023, 20(08): 844-848.
[2] 唐玮, 何融泉, 黄素宁. 深度学习在乳腺癌影像诊疗和预后预测中的应用[J]. 中华乳腺病杂志(电子版), 2023, 17(06): 323-328.
[3] 康夏, 田浩, 钱进, 高源, 缪洪明, 齐晓伟. 骨织素抑制破骨细胞分化改善肿瘤骨转移中骨溶解的机制研究[J]. 中华乳腺病杂志(电子版), 2023, 17(06): 329-339.
[4] 衣晓丽, 胡沙沙, 张彦. HER-2低表达对乳腺癌新辅助治疗疗效及预后的影响[J]. 中华乳腺病杂志(电子版), 2023, 17(06): 340-346.
[5] 施杰, 李云涛, 高海燕. 腋窝淋巴结阳性Luminal A型乳腺癌患者新辅助与辅助化疗的预后及影响因素分析[J]. 中华乳腺病杂志(电子版), 2023, 17(06): 353-361.
[6] 伍秋苑, 陈佩贤, 邓裕华, 何添成, 周丹. 肠道微生物在乳腺癌中的研究进展[J]. 中华乳腺病杂志(电子版), 2023, 17(06): 362-365.
[7] 谭巧, 苏小涵, 侯令密, 黎君彦, 邓世山. 乳腺髓样癌的诊治进展[J]. 中华乳腺病杂志(电子版), 2023, 17(06): 366-368.
[8] 周婉丽, 钱铮, 李喆. 槐耳在乳腺癌免疫治疗中的研究进展[J]. 中华乳腺病杂志(电子版), 2023, 17(06): 369-371.
[9] 熊倩, 罗凤. 乳腺癌患者术后康复现状与对策的研究进展[J]. 中华乳腺病杂志(电子版), 2023, 17(06): 372-374.
[10] 杨小菁, 姜瑞瑞, 石玉香, 王静静, 李长天. 乳腺孤立性纤维性肿瘤一例[J]. 中华乳腺病杂志(电子版), 2023, 17(06): 375-377.
[11] 冯雪园, 韩萌萌, 马宁. 乳腺原发上皮样血管内皮瘤一例[J]. 中华乳腺病杂志(电子版), 2023, 17(06): 378-380.
[12] 康一坤, 袁芃. 三阴性乳腺癌分子遗传学及临床特征研究进展[J]. 中华乳腺病杂志(电子版), 2023, 17(05): 290-293.
[13] 晏晴艳, 雍晓梅, 罗洪, 杜敏. 成都地区老年转移性乳腺癌的预后及生存因素研究[J]. 中华普外科手术学杂志(电子版), 2023, 17(06): 636-638.
[14] 李智铭, 郭晨明, 庄晓晨, 候雪琴, 高军喜. 早期乳腺癌超声造影定性及定量指标的对比研究[J]. 中华普外科手术学杂志(电子版), 2023, 17(06): 639-643.
[15] 钟广俊, 刘春华, 朱万森, 徐晓雷, 王兆军. MRI联合不同扫描序列在胃癌术前分期诊断及化疗效果和预后的评估[J]. 中华消化病与影像杂志(电子版), 2023, 13(06): 378-382.
阅读次数
全文


摘要

版权所有 中华医学会 中华医学电子音像出版社有限责任公司  京ICP备14006079号-1  网络出版服务许可证：(署)网出证(京)字第075号