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

doi:10.3877/cma.j.issn.1674-0807.2019.06.003

Abstract

Abstract:

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

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.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhrxbzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.1674-0807.2019.06.003

https://zhrxbzz.cma-cmc.com.cn/EN/Y2019/V13/I06/331

Figures/Tables 5

References 19

[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.

乳腺癌组织	癌旁正常组织		合计
乳腺癌组织	阳性	阴性	合计
阳性	9	23	32
阴性	0	7	7
合计	9	30	39

乳腺癌组织	癌旁正常组织		合计
乳腺癌组织	阳性	阴性	合计
阳性	9	23	32
阴性	0	7	7
合计	9	30	39

临床病理特征		例数	DNER蛋白表达		检验值	P值
临床病理特征		例数	阳性	阴性	检验值	P值
年龄		?	?	?	?	?
?	≤45岁	24	21(87.5)	3(12.5)	?	0.396^a
?	>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	0.026^a
?	>5 cm	10	10(100)	0(0)	?	?
淋巴结转移		?	?	?	?	?
?	有	26	24(92.3)	2(7.7)	?	0.030^a
?	无	13	8(61.5)	5(38.5)	?	0.030^a
TNM分期		?	?	?	?	?
?	Ⅰ～Ⅱ期	14	8(57.1)	6(42.9)	?	?
?	Ⅲ～Ⅳ期	25	24(96.0)	1(4.0)	?	0.005^a

临床病理特征		例数	DNER蛋白表达		检验值	P值
临床病理特征		例数	阳性	阴性	检验值	P值
年龄		?	?	?	?	?
?	≤45岁	24	21(87.5)	3(12.5)	?	0.396^a
?	>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	0.026^a
?	>5 cm	10	10(100)	0(0)	?	?
淋巴结转移		?	?	?	?	?
?	有	26	24(92.3)	2(7.7)	?	0.030^a
?	无	13	8(61.5)	5(38.5)	?	0.030^a
TNM分期		?	?	?	?	?
?	Ⅰ～Ⅱ期	14	8(57.1)	6(42.9)	?	?
?	Ⅲ～Ⅳ期	25	24(96.0)	1(4.0)	?	0.005^a

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	t＝0.690	0.494
肿瘤直径		?	?	?	?
?	≤2 cm	8	0.356±0.039	?	?
?	>2～5 cm	24	0.811±0.053^a	F＝8.392	0.001
?	>5 cm	7	1.091±0.072^a	?	?
淋巴结转移		?	?	?	?
?	有	28	0.902±0.085	t＝4.925	<0.001
?	无	11	0.426±0.069	t＝4.925	<0.001
TNM分期		?	?	?	?
?	Ⅰ～Ⅱ期	10	0.527±0.058	t＝5.178	<0.001
?	Ⅲ～Ⅳ期	29	0.894±0.075	t＝5.178	<0.001

Please choose a citation manager

Content to export