Bioinformatics-based identification of miR-542-5p as a predictive biomarker in breast cancer therapy.

Bioinformatics-based identification of miR-542-5p as a predictive biomarker in breast cancer therapy.
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基于生物信息学的 miR-542-5p 鉴定作为乳腺癌治疗的预测生物标志物

DOI:
10.1186/s41065-018-0055-7
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发表时间:
2018
期刊:
影响因子:
2.7
通讯作者:
Guo Y
Guo Y
中科院分区:
生物学4区
文献类型:
--
作者:
Zhu QN;Renaud H;Guo Y

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他莫昔芬是雌激素受体α阳性(ERα+)乳腺癌的一线激素治疗。然而,约40%接受他莫昔芬治疗的ERα +乳腺癌患者最终产生耐药性,导致预后不良。本研究的目的是挖掘基因表达综合数据库(GEO)中的可用数据集,包括体外(细胞系)和体内(组织样本),并确定与乳腺癌中他莫昔芬耐药(TamR)相关的所有miRNA。其次,本研究旨在预测新发现的TamR相关miRNAs的关键基因调控网络,并评估miRNAs和靶点作为乳腺癌患者潜在预后生物标志物的潜在作用。使用来自GEO数据库的两个不同研究的微阵列数据集:GSE 66607:MCF-7 TamR细胞的miRNA; 2. GSE 37405:TamR组织。在两个数据集中鉴定了差异表达的microRNA(miRNAs),并且发现5个差异表达的miRNAs在两个数据集之间重叠。使用GSE 37405的图谱和来自Kaplan-Meier绘图仪数据库(KMPD)的数据沿着基因表达谱交互分析(GEPIA)来揭示这5种miRNA与总生存率之间的关系。结果显示,has-miR-542- 5 p是与接受他莫昔芬辅助治疗的ERα +乳腺癌患者的总生存期相关的唯一miRNA。通过米兰达和TargetScan预测has-miR-542- 5 p的靶点,在2个不同的数据库中,3个靶基因酪氨酸3-单加氧酶/色氨酸5-单加氧酶激活蛋白β(YWHAB)、淋巴细胞抗原9(LY 9)和分泌型卷曲相关蛋白1(SFRP 1)的mRNA表达与总生存期相关。在cBioPortal数据库中,SFRP 1的拷贝数改变(CNA)使乳腺癌患者的生存不利,并改变SFRP 1的mRNA表达。本研究提示miRNA has-miR-542- 5 p与TamR相关,可预测乳腺癌患者的预后。此外,has-miR-542- 5 p可能通过涉及靶基因YWHAB、LY 9和SFRP 1的机制起作用。总体而言,has-miR-542- 5 p是乳腺癌患者治疗的预测性生物标志物和潜在靶点。本文的在线版本(10.1186/s41065-018-0055-7)包含补充材料,可供授权用户使用。
Tamoxifen is the first-line hormone therapy for estrogen receptor alpha positive (ERα+) breast cancer. However, about 40% of patients with ERα + breast cancer who receive tamoxifen therapy eventually develop resistance resulting in a poor prognosis. The aim of this study was to mine available data sets in the Gene Expression Omnibus (GEO) database, including in vitro (cell lines) and in vivo (tissue samples), and to identify all miRNAs associated with tamoxifen resistance (TamR) in breast cancer. Secondly, this study aimed to predict the key gene regulatory networks of newly found TamR-related miRNAs and evaluate the potential role of the miRNAs and targets as potential prognosis biomarkers for breast cancer patients. Microarray data sets from two different studies were used from the GEO database: 1. GSE66607: miRNA of MCF-7 TamR cells; 2. GSE37405: TamR tissues. Differentially expressed microRNAs (miRNAs) were identified in both data sets and 5 differentially expressed miRNAs were found to overlap between the two data sets. Profiles of GSE37405 and data from the Kaplan-Meier Plotter Database (KMPD) along with Gene Expression Profiling Interactive Analysis (GEPIA) were used to reveal the relationship between these 5 miRNAs and overall survival. The results showed that has-miR-542-5p was the only miRNA associated with overall survival of ERα + breast cancer patients who received adjuvant tamoxifen. Targets of has-miR-542-5p were predicted by miRanda and TargetScan, and the mRNA expression of the three 3 target gene, Tyrosine 3-Monooxygenase/Tryptophan 5-Monooxygenase Activation Protein Beta (YWHAB), Lymphocyte Antigen 9 (LY9), and Secreted Frizzled Related Protein 1 (SFRP1) were associated with overall survival in 2 different databases. Copy-number alterations (CNAs) of SFRP1 confer survival disadvantage to breast cancer patients and alter the mRNA expression of SFRP1 in cBioPortal database. This study indicates that miRNA has-miR-542-5p is associated with TamR and can predict prognosis of breast cancer patients. Furthermore, has-miR-542-5p may be acting through a mechanism involving the target genes YWHAB, LY9, and SFRP1. Overall, has-miR-542-5p is a predictive biomarker and potential target for therapy of breast cancer patients. The online version of this article (10.1186/s41065-018-0055-7) contains supplementary material, which is available to authorized users.
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