[1]姜黄,郑丽华,徐小艳,等.细胞外基质金属蛋白酶诱导因子、基质金属蛋白酶-9和赖氨酸去甲基化酶6B在浸润性乳腺癌组织中的表达及其病理诊断价值[J].新乡医学院学报,2024,(2):143-150.[doi:10.7683/xxyxyxb.2024.02.008]
　JIANG Huang,ZHENG Lihua,XU Xiaoyan,et al.Expression and pathological diagnostic value of extracellular matrix metalloproteinase inducer,matrix metalloproteinase-9 and lysine demethylase 6B in invasive breast cancer[J].Journal of Xinxiang Medical University,2024,(2):143-150.[doi:10.7683/xxyxyxb.2024.02.008]
点击复制

细胞外基质金属蛋白酶诱导因子、基质金属蛋白酶-9和赖氨酸去甲基化酶6B在浸润性乳腺癌组织中的表达及其病理诊断价值
分享到：

《新乡医学院学报》[ISSN:1004-7239/CN:41-1186/R]

卷:
期数:
2024年2
页码:
143-150
栏目:
临床研究
出版日期:
2024-02-05

文章信息/Info

Title:
Expression and pathological diagnostic value of extracellular matrix metalloproteinase inducer,matrix metalloproteinase-9 and lysine demethylase 6B in invasive breast cancer
作者:
姜黄1; 郑丽华2; 徐小艳1; 王建君1; 徐宪伟1; 王娜1; 邢晨菊1; 鲁显宇1
（1.河南中医药大学第五临床医学院/郑州人民医院病理科，河南　郑州　450003；2.河南医学高等专科学校人体解剖学教研室，河南　郑州　450000）
Author(s):
JIANG Huang1; ZHENG Lihua2; XU Xiaoyan1; WANG Jianjun1; XU Xianwei1; WANG Na1; XING Chenju1; LU Xianyu1
(1.Department of Pathology,the Fifth Clinical Medical College of Henan University of Chinese Medicine/People′s Hospital of Zhengzhou,Zhengzhou 450003,Henan Province,China;2.Teaching and Research Office of Human Anatomy,Henan Medical College,Zhengzhou 450000,Henan Province,China)
关键词:
浸润性乳腺癌; 细胞外基质金属蛋白酶诱导因子; 基质金属蛋白酶-9; 赖氨酸去甲基化酶6B; 临床病理特征; 诊断价值
Keywords:
invasive breast cancer; extracellular matrix metalloproteinase inducer; matrix metalloproteinase-9; lysine demethylase 6B; clinicopathologic features; diagnostic value
分类号:
R361.2
DOI:
10.7683/xxyxyxb.2024.02.008
文献标志码:
A
摘要:
目的　探讨浸润性乳腺癌组织中细胞外基质金属蛋白酶诱导因子（EMMPRIN）、基质金属蛋白酶-9(MMP-9）和赖氨酸去甲基化酶6B（KDM6B）蛋白的表达及其与临床病理特征的关系，并分析3种蛋白的相关性及其在浸润性乳腺癌病理诊断中的价值。
方法　选择2014年1月至2017年12月河南中医药大学第五临床医学院/郑州人民医院病理科保存的124例浸润性乳腺癌患者的手术切除活检标本为研究对象，另选取同期保存的低级别导管内癌组织标本20例、高级别导管内癌组织标本27例、距离浸润性乳腺癌>1 cm 处癌旁组织标本22例作为对照组。采用免疫组织化学法检测乳腺癌旁组织、低级别导管内癌、高级别导管内癌及浸润性乳腺癌组织中EMMPRIN、MMP-9和KDM6B蛋白的表达。分析EMMPRIN、MMP-9和KDM6B蛋白的相对表达量与浸润性乳腺癌临床病理特征的关系；采用Spearman法分析浸润性乳腺癌组织中EMMPRIN、MMP-9、KDM6B 蛋白的相关性，受试者操作特征（ROC）曲线评估EMMPRIN、MMP-9和KDM6B蛋白对浸润性乳腺癌的诊断价值。
结果　高级别导管内癌和浸润性乳腺癌组织中EMMPRIN、MMP-9蛋白的相对表达量显著高于乳腺癌旁组织和低级别导管内癌组织（P<0.05），KDM6B蛋白的相对表达量显著低于癌旁组织和低级别导管内癌组织（P<0.05）；浸润性乳腺癌组织中EMMPRIN、MMP-9蛋白的相对表达量显著高于高级别导管内癌组织（P<0.05），KDM6B蛋白的相对表达量显著低于高级别导管内癌组织（P<0.05）；癌旁组织与低级别导管内癌组织中EMMPRIN、MMP-9和KDM6B蛋白的相对表达量比较差异无统计学意义（P>0.05）。EMMPRIN、KDM6B蛋白相对表达量与浸润性乳腺癌患者的年龄、肿瘤部位和肿瘤直径无关（P>0.05），MMP-9蛋白相对表达量与浸润性乳腺癌患者的年龄和肿瘤部位无关（P>0.05）。EMMPRIN、MMP-9和KDM6B蛋白的相对表达量与浸润性乳腺癌的世界卫生组织（WHO）分级、淋巴结转移、TNM 分期有关（P<0.05），MMP-9蛋白的相对表达量与浸润性乳腺癌的肿瘤直径有关（P<0.05）。浸润性乳腺癌WHO分级Ⅰ级、Ⅱ级、Ⅲ级中，EMMPRIN、MMP-9蛋白的相对表达量依次升高，KDM6B蛋白的相对表达量依次降低（P<0.05）；浸润性乳腺癌淋巴结有转移组EMMPRIN、MMP-9蛋白的相对表达量显著高于无淋巴结转移组（P<0.05），KDM6B蛋白的相对表达量显著低于无淋巴结转移组（P<0.05）；TNM分期 Ⅲ~Ⅳ期组 EMMPRIN、MMP-9蛋白的相对表达量显著高于Ⅰ~Ⅱ期组（P<0.05），KDM6B蛋白的相对表达量显著低于Ⅰ~Ⅱ期组（P<0.05）。在浸润性乳腺癌肿瘤直径≤2 cm、2~5 cm、>5 cm组中MMP-9蛋白的相对表达量依次升高（P<0.05）。Spearman相关性分析显示，浸润性乳腺癌组织中EMMPRIN与MMP-9蛋白的表达呈显著正相关（r=0.990，P=0.000），EMMPRIN与KDM6B蛋白的表达呈显著负相关（r=-0.606，P=0.000），MMP-9与KDM6B蛋白的表达呈显著负相关（r=-0.612，P=0.000）。ROC曲线分析显示，EMMPRIN蛋白诊断浸润性乳腺癌的曲线下面积（AUC）为0.875［95%置信区间（CI）:0.823~0.926，P<0.05］，最佳界值为10.043，敏感度为 79.0%，特异度为76.8%；MMP-9蛋白诊断浸润性乳腺癌的AUC为0.863（95%CI：0.808~0.917，P<0.05），最佳界值为10.070，敏感度为74.2%，特异度为76.8%；KDM6B蛋白诊断浸润性乳腺癌的AUC为0.267（95%CI：0.196~0.338，P<0.05），最佳界值为11.003，敏感度为71.0%，特异度为98.6%。
结论　EMMPRIN、MMP-9和KDM6B蛋白与浸润性乳腺癌的发生发展有关，检测EMMPRIN、MMP-9和KDM6B蛋白的表达有助于浸润性乳腺癌的病理诊断及其浸润转移的临床判断。
Abstract:
Objective　To investigate the expressions of extracellular matrix metalloproteinase inducer (EMMPRIN),matrix metalloproteinase-9 (MMP-9),lysine demethylase 6B (KDM6B) proteins and their correlation with clinicopathologic features in invasive breast cancer,and analyze the correlation among the three proteins and their value in pathological diagnosis of invasive breast cancer.
Methods　The surgical biopsy specimens of 124 patients with invasive breast cancer who were admitted to the Department of Pathology,the Fifth Clinical Medical College of Henan University of Chinese Medicine/People′s Hospital of Zhengzhou from January 2014 to December 2017 were selected as research subjects,and 20 low-grade intraductal carcinoma tissue specimens,27 high-grade intraductal carcinoma tissue specimens,and 22 adjacent tissue specimens >1 cm away from the invasive breast cancer were selected as controls.The expressions of EMMPRIN,MMP-9 and KDM6B proteins in cancer-adjacent tissues,low-grade intraductal carcinoma tissues,high-grade intraductal carcinoma tissues and invasive breast cancer tissues were detected by immunohistochemistry.The relationship between the relative expressions of EMMPRIN,MMP-9 and KDM6B proteins and clinicopathologic features of invasive breast cancer was analyzed,Spearman correlation analysis was used to evaluate the correlation of EMMPRIN,MMP-9 and KDM6B proteins in breast cancer tissues,and receiver operating characteristic (ROC) curve was adopted to evaluate the diagnostic value of EMMPRIN,MMP-9 and KDM6B for invasive breast cancer.
Results　The relative expressions of EMMPRIN and MMP-9 proteins in high-grade intraductal carcinoma and invasive breast cancer tissues were significantly higher those in cancer-adjacent tissues and low-grade intraductal carcinoma tissues,and the relative expression of KDM6B protein was significantly lower than those in cancer-adjacent tissues and low-grade intraductal carcinoma tissues (P<0.05);the relative expressions of EMMPRIN and MMP-9 proteins in invasive breast cancer tissues were significantly higher those in high-grade intraductal carcinoma tissues,and the relative expression of KDM6B protein was significantly lower than that in high-grade intraductal carcinoma tissues (P<0.05);there was no statistically significant difference in the relative expressions of EMMPRIN,MMP-9 and KDM6B proteins between cancer-adjacent tissues and low-grade intraductal carcinoma tissues (P>0.05).The relative expressions of EMMPRIN and KDM6B proteins were not related to the age,tumor location and tumor diameter of patients with invasive breast cancer (P>0.05),and the relative expression of MMP-9 protein was not related to the age and tumor location of patients with invasive breast cancer (P>0.05).Relative expressions of EMMPRIN,MMP-9 and KDM6B proteins were correlated with WHO grading,lymph node metastasis,and tumor,node and metastasis (TNM) staging of invasive breast cancer (P<0.05),and the relative expression of MMP-9 protein was correlated with the tumor diameter(P<0.05).In the WHO grades I,II,and III of invasive breast cancer,the relative expressions of EMMPRIN and MMP-9 proteins increased sequentially,while the relative expression of KDM6B protein decreased sequentially (P<0.05);the relative expressions of EMMPRIN and MMP-9 proteins in the lymph node metastasis group were significantly higher than those in the non-lymph node metastasis group,and the relative expression of KDM6B protein was significantly lower than that in the non-lymph node metastasis group (P<0.05);the relative expressions of EMMPRIN and MMP-9 proteins in TNM stages III-IV were significantly higher than those in stages I-II (P<0.05),while the relative expression of KDM6B protein was significantly lower than that in stages I-II (P<0.05).In the group of invasive breast cancer with diameter ≤ 2 cm,2 to 5 cm,and >5 cm,the relative expression of MMP-9 protein increased sequentially (P<0.05).Spearman correlation analysis showed that the expression of EMMPRIN was positively correlated with MMP-9 protein in invasive breast cancer tissues (r=0.990,P=0.000),the expression of EMMPRIN was negatively correlated with KDM6B protein (r=-0.606,P=0.000),and the expression of MMP-9 was negatively correlated with KDM6B protein (r=-0.612,P=0.000).ROC curve analysis showed that the area under the curve (AUC) of EMMPRIN protein for diagnosing invasive breast cancer was 0.875 ［95% confidence interval (CI):0.823-0.926,P<0.05］,with an optimal threshold of 10.043,sensitivity of 79.0%,and specificity of 76.8%;the AUC of MMP-9 protein in diagnosing invasive breast cancer was 0.863 (95%CI:0.808-0.917,P<0.05),with an optimal threshold of 10.070,sensitivity of 74.2%,and specificity of 76.8%;the AUC of KDM6B protein in diagnosing invasive breast cancer was 0.267 (95%CI:0.196-0.338,P<0.05),with an optimal threshold of 11.003,sensitivity of 71.0%,and specificity of 98.6%.
Conclusion　EMMPRIN,MMP-9 and KDM6B are related to the occurrence and development of invasive breast cancer.Detection of the expressions of EMMPRIN,MMP-9 and KDM6B is helpful to the pathological diagnosis of invasive breast cancer and clinical judgment of invasion and metastasis of breast cancer.

参考文献/References:

［1］　中国抗癌协会乳腺癌专业委员会.中国乳腺癌筛查与早期诊断指南［J］.中国癌症杂志,2022,32(4):363-372.
THE SOCIETY OF BREAST CANCER,CHINA ANTICANCER ASSOCIATION.Screening and early diagnosis of breast cancer in China:a practice guideline［J］.China Oncol,2022,32(4):363-372.
［2］　ZHANG N,LIU Z,LAI X,et al.Silencing of CD147 inhibits cell proliferation,migration,invasion,lipid metabolism dysregulation and promotes apoptosis in lung adenocarcinoma via blocking the Rap1 signaling pathway［J］.Respir Res,2023,24(1):253-265.
［3］　CHO H J,JUNG H J.Cyclophilin A inhibitors suppress proliferation and induce apoptosis of MKN45 gastric cancer stem-like cells by regulating CypA/CD147-mediated signaling pathway［J］.Int J Mol Sci,2023,24(5):4734-4748.
［4］　SHI M Y,WANG Y,SHI Y,et al.SETDB1-mediated CD147-K71 di-methylation promotes cell apoptosis in non-small cell lung cancer［J］.Genes Dis,2023,11(2):978-992.
［5］　YAN C,SUN C,LU D,et al.Estimation of associations between MMP9 gene polymorphisms and breast cancer:evidence from a meta-analysis［J］.Int J Biol Markers,2022,37(1):13-20.
［6］　DU L,DAI B,LIU X,et al.KDM6B regulates M2 polarization of macrophages by modulating the stability of nuclear β-catenin［J］.Biochim Biophys Acta Mol Basis Dis,2023,1869(2):166611.
［7］　梅放,柳剑英,薛卫成.浸润性乳腺癌的组织学分级:Nottingham组织学分级系统［J］.中华病理学杂志,2019,48(8):659-664.
MEI F,LIU J Y,XUE W C.Histological grading of invasive breast carcinoma:Nottingham histological grading system［J］.Chin J Pathol,2019,48(8):659-664.
［8］　徐小艳,王建君,王慧,等.JMJD3和Ki-67定量检测与浸润性乳腺导管癌分子分型及临床病理学特征的关系［J］.中国癌症杂志,2020,30(1):57-63.
XU X Y,WANG J J,WANG H,et al.Quantitative detection of JMJD3 and Ki-67 in invasive ductal carcinoma of breast and their relationship with molecular typing and clinicopathological features［J］.China Oncol,2020,30(1):57-63.
［9］　王璐，刘敏.乳腺癌患者血清中B7-同源物2和B7-同源物3的表达及临床意义［J］.新乡医学院学报，2022,39(9):827-832.
WANG L,LIU M.Expression and clinical significance of B7 homolog 2 and B7 homolog 3 in serum of breast of patients with breast cancer［J］.J Xinxiang Med Univ,2022,39(9):827-832.
［10］　ZHANG Z,LIU X,YANG X,et al.Identification of faecalextracellular vesicles as novel biomarkers for the non-invasive diagnosis and prognosis of colorectal cancer［J］.J Extracell Vesicles,2023,12(1):e12300.
［11］　LIAO C G,LIANG X H,KE Y,et al.Active demethylation upregulates CD147 expression promoting non-small cell lung cancer invasion and metastasis［J］.Oncogene,2022,41(12):1780-1794.
［12］　KSTERS N,GRUPP K,GRASS J K,et al.CD147 expression lacks prognostic relevance in esophageal cancer［J］.J Cancer Res Clin Oncol,2022,148(4):837-844.
［13］　王建君,徐小艳,冯智坤,等.乳腺癌中PTEN和Basigin1蛋白的表达与其临床病理学特征的关系［J］.中国普外基础与临床杂志,2020,27(7):825-830.
WANG J J,XU X Y,FENG Z K,et al.The relationship between the expression of PTEN/Basigin1 protein and clinicopathological features in breast cancer［J］.Chin J Bases Clin Gen Surg,2020,27(7):825-830.
［14］　FARHANA A,ALSRHANI A,NAZAM N,et al.Gold nanoparticles inhibit PMA-induced MMP-9 expression via microRNA-204-5p upregulation and deactivation of NF-κBp65 in breast cancer cells［J］.Biology,2023,12(6):777.
［15］　SHAKERY T,SAFARI F.Downregulation of pinkbar/pAKT and MMP2/MMP9 expression in MDA-MB-231 breast cancer cells as potential targets in cancer therapy by hAMSCs secretome［J］.Cells Tissues Organs,2023,212(2):155-163.
［16］　胡楠,邓力,包旭,等.组蛋白去甲基化酶JMJD3对乳腺癌干细胞的影响［J］.华西药学杂志,2018,33(5):485-489.
HU N,DENG L,BAO X,et al.Effects of a histone demethylase JMJD3 on the breast cancer stem cells［J］.West China J Pharm Sci,2018,33(5):485-489.
［17］　吕娟,吕珊妹,董学君.JMJD3和CD163在乳腺癌中的表达及其临床意义［J］.医学研究杂志,2022,51(1):116-119,128.
LYU J,LYU S M,DONG X J.Expression and clinical significance of JMJD3 and CD163 in breast cancer［J］.J Med Res,2022,51(1):116-119,128.
［18］　LI F,ZHANG J,GUO J,et al.RNA interference targeting CD147 inhibits metastasis and invasion of human breast cancer MCF-7 cells by downregulating MMP-9/VEGF expression［J］.Acta Biochim Biophys Sin,2018,50(7):676-684.
［19］　ASGARI R,MANSOURI K,BAKHTIARI M,et al.CD147 as an apoptosis regulator in spermatogenesis:deciphering its association with matrix metalloproteinases pathway［J］.Mol Biol Rep,2019(40):1099-1105.
［20］　朱长龙，王晓琼，何常.结直肠癌中HIF-1α、CD147和MMP-9表达与临床病理特征的关系［J］.贵州医科大学学报,2020,45(4):466-471.
ZHU C L,WANG X Q,HE C.Correlation between expression of HIF-1α,CD147 and MMP-9 and clinicopathological features in colorectal cancer［J］.J Guizhou Med Univ,2020,45(4):466-471.
［21］　徐小艳,徐宪伟,王慧,等.肺腺癌中CD147、MMP-9和VEGF的表达及临床意义［J］.临床与实验病理学杂志,2017,33(4):384-387.
XU X Y,XU X W,WANG H,et al.Quantitative expression of CD147,MMP-9 and VEGF in lung adenocarcinoma and their clinical significance［J］.Chin J Clin Exp Pathol,2017,33(4):384-387.
［22］　吴狄,邓海媚,姚睿智,等.前列腺癌中CD147、MMP-2 mRNA表达与临床分期、病理学分级的关系［J］.分子诊断与治疗杂志,2021,13(5):824-827.
WU D,DENG H M,YAO R Z,et al.Relationship between the expression of CD147,MMP-2 mRNA and clinical stage and pathological grade in prostate cancer［J］.J Mol Diagn Ther,2021,13(5):824-827.
［23］　YU B,ZHANG Y,WU K,et al.CD147 promotes progression of head and neck squamous cell carcinoma via NF-kappa B signaling［J］.J Cell Mol Med,2019,23(2):954-966.
［24］　PARK W Y,HONG B J,LEE J,et al.H3K27 demethylase JMJD3 employs the NF-κB and BMP signaling pathways to modulate the tumor microenvironment and promote melanoma progression and metastasis［J］.Cancer Res,2016,76(1):161-170.
［25］　GUARNERI C,BEVELACQUA V,POLESEL J,et al.NF-κB inhibition is associated with OPN/MMP-9 downregulation in cutaneous melanoma［J］.Oncol Rep,2017,37(2):737-746.

相似文献/References:

[1]毛淑平,武文杰,王　苏,等.绝经前后女性浸润性乳腺癌危险因素分析[J].新乡医学院学报,2022,39(2):127.[doi:10.7683/xxyxyxb.2022.02.005]
　MAO Shuping,WU Wenjie,WANG Su,et al.Risk factors for invasive breast cancer in premenopausal and postmenopausal women[J].Journal of Xinxiang Medical University,2022,39(2):127.[doi:10.7683/xxyxyxb.2022.02.005]

更新日期/Last Update: 2024-02-05