Peng Hai-Tao, Chen Jian, Liu Tian-Yu, Wu Yan-Qing, Lin Xiao-Hong, Lai Yuan-Hui, Huang Ying-Feng
Department of General Surgery, Guangzhou First People's Hospital, Guangzhou Medical University Guangzhou 510180, Guangdong, China.
Department of General Surgery, Guangzhou Twelfth People's Hospital, Guangzhou Medical University Guangzhou 510620, Guangdong, China.
Int J Clin Exp Pathol. 2017 Nov 1;10(11):10852-10862. eCollection 2017.
Glyoxalase 1 (Glo1) is an enzyme that plays a role to metabolize and inactivate methylglyoxal. Previous studies also have confirmed that Glo1 is closely related with tumorigenesis, metastasis, and drug-resistant, but its prognostic value in breast cancer has never been explored. In this study, we investigated the expression of Glo1 in breast cancer cell lines and tissues using real-time PCR, western blot and immunohistochemical analysis. We found Glo1 was frequently up-regulated in human breast cancer cells and tissues, and high expression of Glo1 was associated with positive lymph node, lymphovascular invasion, and TNM stage (all <0.05). The Kaplan-Meier survival curve demonstrated that patients with high Glo1 expression had a shorter overall survival (OS) and recurrence-free survival (RFS) (Both <0.001) than those with low Glo1 expression. Moreover, the univariate and further multivariate analysis revealed that Glo1 expression was an independent prognostic factor for both OS and RFS of breast cancer patients. Next, with CCK-8 assay, cell apoptosis analysis, colony formation assay, transwell invasion/migration assay, and wound-healing assay, we validated knock-down of Glo1 suppressed invasion and migration and promoted apoptosis of breast cancer cells. Taken together, we demonstrated the tumor-promoter Glo1 may serve as a prognostic biomarker for breast cancer.
乙二醛酶1(Glo1)是一种在甲基乙二醛的代谢和失活过程中发挥作用的酶。先前的研究也证实,Glo1与肿瘤发生、转移和耐药性密切相关,但其在乳腺癌中的预后价值尚未得到探索。在本研究中,我们使用实时PCR、蛋白质免疫印迹和免疫组织化学分析,研究了Glo1在乳腺癌细胞系和组织中的表达情况。我们发现,Glo1在人乳腺癌细胞和组织中经常上调,Glo1的高表达与阳性淋巴结、淋巴管浸润和TNM分期相关(均P<0.05)。Kaplan-Meier生存曲线表明,Glo1高表达的患者总生存期(OS)和无复发生存期(RFS)均短于Glo1低表达的患者(均P<0.001)。此外,单因素和进一步的多因素分析显示,Glo1表达是乳腺癌患者OS和RFS的独立预后因素。接下来,通过CCK-8检测、细胞凋亡分析、集落形成检测、Transwell侵袭/迁移检测和伤口愈合检测,我们证实敲低Glo1可抑制乳腺癌细胞的侵袭和迁移,并促进其凋亡。综上所述,我们证明了肿瘤促进因子Glo1可能作为乳腺癌的一种预后生物标志物。