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MAT1 correlates with molecular subtypes and predicts poor survival in breast cancer

查看全文 作  者:Hanxiao [1]Xu;Xianguang [2]Bai;Shengnan [1]Yu;Qian [1]Liu;Richard G [3]Pestell;Kongming [1]Wu 高影响力作者 机构地区:[1]Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China;[2]Medical School of Pingdingshan University, Pingdingshan 467000, China;[3]Pennsylvania Center for Cancer and Regenerative Medicine, Wynnewood, PA 19096, USA高影响力机构 出  处:《Chinese Journal of Cancer Research》索引2018年第30卷第3期,共13页高影响力期刊 基  金:supported by the National Natural Science Foundation of China (Grant No.81572608 and 81172422);the Wuhan Science and Technology Bureau (Grant No.2017060201010170) 摘  要:Objective:Menage a trois 1(MAT1)is a targeting subunit of cyclin-dependent kinase-activating kinase and general transcription factor IIH kinase,which modulates cell cycle,transcription and DNA repair.Its dysregulation is responsible for diseases including cancers.To further explore the role of MAT1 in breast cancer,we investigated the pathways in which MAT1 might be involved,the association between MAT1 and molecular subtypes,and the role of MAT1 in clinical outcomes of breast cancer patients.Methods:We conducted immunohistochemistry staining on tissue microarray and immunofluorescence staining on sections of MAT1 stable breast cancer cells.Also,we performed Kyoto Encyclopedia of Genes and Genomes pathway analysis,correlation analysis and prognosis analysis on public databases.Results:MAT1 was involved in multiple pathways including normal physiology signaling and disease-related signaling.Furthermore,MAT1 positively correlated with the protein status of estrogen receptor and progesterone receptor,and was enriched in luminal-type and human epidermal growth factor receptor 2-enriched breast cancer in comparison with basal-like subtype at both m RNA and protein levels.Correlation analysis revealed significant association between MAT1 m RNA amount and epithelial markers,mesenchymal markers,cancer stem cell markers,apoptosis markers,transcription markers and oncogenes.Consistently,the results of immunofluorescence stain indicated that MAT1 overexpression enhanced the protein abundance of epidermal growth factor receptor,vimentin,sex determining region Y-box 2 and sine oculis homeobox homolog 1.Importantly,Kaplan-Meier Plotter analysis reflected that MAT1 could serve as a prognostic biomarker predicting worse relapse-free survival and metastasis-free survival.Conclusions:MAT1 is correlated with molecular subtypes and is associated with unfavorable prognosis for breast cancer patients. 关 键 词:子类型 分子 预言 CYCLIN 子单元 DNA
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