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乳腺癌中基质金属蛋白酶潜在治疗靶点的综合生物信息学分析

An integrated bioinformatics analysis of potential therapeutic targets among matrix metalloproteinases in breast cancer.

作者信息

Xia Haiqun, Yu Weixuan, Liu Ming, Li Hong, Pang Wei, Wang Libin, Zhang Yunda

机构信息

Department of Radiation Oncology, Tungwah Hospital of Sun Yat-Sen University, Dongguan, Guangdong 523000, P.R. China.

Department of Surgical Oncology, Tungwah Hospital of Sun Yat-Sen University, Dongguan, Guangdong 523000, P.R. China.

出版信息

Oncol Lett. 2019 Sep;18(3):2985-2994. doi: 10.3892/ol.2019.10669. Epub 2019 Jul 26.

Abstract

Breast cancer (BC) is one of the most aggressive malignancies worldwide among females. Matrix metalloproteinases (MMPs), as the most abundant class of non-serine proteases present in invasive and metastatic tumors, can regulate a variety of alterations in the microenvironment during tumor progression. However, the differential expression of MMPs and its prognostic values in BC is yet to be elucidated. In this research, using the ONCOMINE dataset, The Cancer Genome Atlas, Breast Cancer Gene-Expression Miner v4.1 (Bc-GenExMiner), Kaplan-Meier Plotter and cBioPortal, the transcriptional MMPs and survival outcome data of patients with BC was compared. It was indicated that mRNA levels of MMP1/3/9/10/11/12/13 were increased compared with non-tumor tissues, whereas mRNA expression of MMP2/16/19/23B/28 was lower in BC tissues. Kaplan-Meier plots showed that high mRNA levels of MMP2/10/16/19/20/23B/27 in patients with BC were associated with better recurrence-free survival. In contrast, high MMP1/8/9/11/12 conferred worse RFS rate. Meanwhile, high transcription levels of MMP1/3/11/12/13 predicted shorter distant metastasis-free survival, while high levels of MMP1/12 demonstrated worse overall survival in patients with BC. From Bc-GenExMiner, it was indicated that high expression of MMP16/20 was correlated with better prognosis, while MMP1/9/11/12/13/14/15 exerted a negative effect on patient prognosis. The integrative bioinformatics analysis performed in the present study suggests that MMP1/9/12/16, compared with other MMPs, are potentially appropriate targets for targeted therapy in patients with BC.

摘要

乳腺癌(BC)是全球女性中最具侵袭性的恶性肿瘤之一。基质金属蛋白酶(MMPs)作为侵袭性和转移性肿瘤中存在的最丰富的非丝氨酸蛋白酶类别,可在肿瘤进展过程中调节微环境中的多种改变。然而,MMPs在BC中的差异表达及其预后价值尚未阐明。在本研究中,使用ONCOMINE数据集、癌症基因组图谱、乳腺癌基因表达挖掘器v4.1(Bc-GenExMiner)、Kaplan-Meier绘图仪和cBioPortal,比较了BC患者的转录MMPs和生存结果数据。结果表明,与非肿瘤组织相比,MMP1/3/9/10/11/12/13的mRNA水平升高,而BC组织中MMP2/16/19/23B/28的mRNA表达较低。Kaplan-Meier绘图显示,BC患者中MMP2/10/16/19/20/23B/27的高mRNA水平与更好的无复发生存率相关。相反,高MMP1/8/9/11/12导致更差的无复发生存率。同时,MMP1/3/11/12/13的高转录水平预示着无远处转移生存期较短,而高水平的MMP1/12表明BC患者的总生存期较差。从Bc-GenExMiner可知,MMP16/20的高表达与较好的预后相关,而MMP1/9/11/12/13/14/15对患者预后有负面影响。本研究进行的综合生物信息学分析表明,与其他MMPs相比,MMP1/9/12/16可能是BC患者靶向治疗的合适靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/424e/6704324/1be1c364c684/ol-18-03-2985-g00.jpg

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