Xu Xiaoyan, Wang Jianjun, Yan Chen, Men Yingli, Jiang Huang, Fang Huijuan, Xu Xianwei, Yang Jinhua
Department of Pathology, People's Hospital of Zhengzhou, Zhengzhou 450000, China.
Academician Workstation, People's Hospital of Zhengzhou, Zhengzhou 450000, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2020 Nov 30;40(11):1593-1600. doi: 10.12122/j.issn.1673-4254.2020.11.09.
To examine the expressions of JMJD3, matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) in invasive ductal breast carcinoma, their association with the clinicopathological features of the patients and the effect of JMJD3 overexpression on proliferation and MMP-2 and VEGF expressions in breast cancer cells.
The protein and mRNA expressions of JMJD3, MMP-2, and VEGF in invasive ductal breast carcinoma and paired adjacent tissues were detected by immunohistochemistry and RT-PCR, respectively, and their correlation with the clinicopathological characteristics of the patients was analyzed. Kaplan-Meier survival analysis was used to evaluate the correlation of JMJD3, MMP-2 and VEGF expression levels with the survival of the patients. In breast cancer MDA-MB-231 cells transfected with a JMJD3-expression plasmid, the expression of Ki67 was examined immunohistochemically, the cell proliferation was assessed with CCK8 assay, and the mRNA expressions of MMP-2 and VEGF were detected with RT-PCR.
Breast cancer tissues had significantly lower JMJD3 expression and higher MMP-2 and VEGF expressions at both the mRNA and protein levels than the adjacent tissue ( < 0.05). The positivity rates of JMJD3, MMP-2 and VEGF in breast cancer tissues were significantly correlated with tumor diameter, differentiation, TNM stage, lymph node metastasis, and molecular subtypes ( < 0.05). KaplanMeier analysis showed that JMJD3 expression level was positively while MMP-2 and VEGF were inversely correlated with the disease-free survival time of the patients ( < 0.05). Cox regression analysis identified JMJD3, MMP-2, VEGF and tumor differentiation as independent prognostic factors of breast cancer. Spearman correlation analysis suggested a negative correlation of JMJD3 with MMP2 (=-0.569, < 0.05) and VEGF (=-0.533, < 0.05) and a positive correlation between MMP2 and VEGF (=0.923, < 0.05). In MDA-MB-231 cells, overexpression of JMJD3 inhibited the proliferation of MDA-MB-231 cells and the expression of MMP-2 and VEGF.
The expressions of JMJD3, MMP-2 and VEGF in invasive ductal breast carcinoma are closely correlated to tumor proliferation, invasion, metastasis and prognosis and can be used for prognostic evaluation of breast cancer.
检测组蛋白赖氨酸去甲基化酶3（JMJD3）、基质金属蛋白酶-2（MMP-2）和血管内皮生长因子（VEGF）在乳腺浸润性导管癌中的表达，分析其与患者临床病理特征的关系，以及JMJD3过表达对乳腺癌细胞增殖及MMP-2和VEGF表达的影响。
分别采用免疫组织化学法和逆转录-聚合酶链反应（RT-PCR）检测乳腺浸润性导管癌组织及其配对癌旁组织中JMJD3、MMP-2和VEGF的蛋白及mRNA表达，并分析其与患者临床病理特征的相关性。采用Kaplan-Meier生存分析法评估JMJD3、MMP-2和VEGF表达水平与患者生存的相关性。在转染JMJD3表达质粒的乳腺癌MDA-MB-231细胞中，免疫组织化学检测Ki67的表达，CCK8法检测细胞增殖，RT-PCR检测MMP-2和VEGF的mRNA表达。
乳腺癌组织中JMJD3的mRNA和蛋白表达水平均显著低于癌旁组织，而MMP-2和VEGF的表达则显著高于癌旁组织（P<0.05）。乳腺癌组织中JMJD3、MMP-2和VEGF的阳性率与肿瘤直径、分化程度、TNM分期、淋巴结转移及分子亚型均显著相关（P<0.05）。Kaplan-Meier分析显示，JMJD3表达水平与患者无病生存时间呈正相关，而MMP-2和VEGF与患者无病生存时间呈负相关（P<0.05）。Cox回归分析确定JMJD3、MMP-2、VEGF及肿瘤分化程度为乳腺癌的独立预后因素。Spearman相关性分析提示JMJD3与MMP-2（r=-0.569，P<0.05）及VEGF（r=-0.533，P<0.05）呈负相关，MMP-2与VEGF呈正相关（r=0.923，P<0.05）。在MDA-MB-231细胞中，JMJD3过表达抑制了MDA-MB-231细胞的增殖及MMP-2和VEGF的表达。
JMJD3、MMP-2和VEGF在乳腺浸润性导管癌中的表达与肿瘤增殖、侵袭、转移及预后密切相关，可用于乳腺癌的预后评估。
