Clinical Relevance of microRNA Expressions in Breast Cancer Validated Using the Cancer Genome Atlas (TCGA).

Clinical Relevance of microRNA Expressions in Breast Cancer Validated Using the Cancer Genome Atlas (TCGA).
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DOI:
10.1245/s10434-017-5984-2
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发表时间:
2017-10
影响因子:
3.7
通讯作者:
Takabe K
Takabe K
中科院分区:
医学2区
文献类型:
--
作者:
Kim SY;Kawaguchi T;Yan L;Young J;Qi Q;Takabe K

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MicroRNAs(miRNAs)在乳腺癌的发生、发展过程中起着重要作用。miRNA-205具有肿瘤抑制特性,而miRNA-18 a具有致癌和肿瘤抑制作用。miRNA-744在乳腺癌中的作用尚不清楚,但在体外具有肿瘤抑制作用。我们假设所有三种miRNAs的高表达与更好的生存率相关,这是基于它们在乳腺癌中的已知功能。所有数据均来自癌症基因组图谱(TCGA)。从Genomic Data Commons(GDC)数据门户检索miRNA-18a、miRNA-205和miRNA-744的表达用于分析。在推导出miRNA特异性阈值并用于将患者分为高表达组或低表达组后,使用考克斯比例风险模型计算生存数据。基于受体状态和AJCC第7版TNM分期对患者进行进一步的亚组分析。在TCGA中记录的1052/1097个样品具有关于感兴趣的miRNA的临床数据和miRNA序列数据集。miRNA-18a(p = 0.079)、miRNA-205(p = 0.034)和miRNA-744(p = 0.0135)的高表达与更好的生存相关。在亚组分析中,雌激素受体(ER)、孕激素受体(PR)阳性和淋巴结阴性疾病具有统计学显著的生存优势,miRNA-18 a、miRNA-205和miRNA-744高表达。通过利用具有足够统计功效的大数据集(TCGA),我们发现乳腺肿瘤样本中miRNA-18a、miRNA-205和miRNA-744的高表达均与ER/PR阳性、淋巴结阴性疾病的更好总生存率相关,支持它们作为乳腺癌肿瘤抑制因子的作用。
MicroRNAs (miRNAs) play a critical role in the carcinogenesis and progression of breast cancer. MiRNA-205 has tumor suppressive properties, whereas miRNA-18a has both oncogenic and tumor suppressive roles. MiRNA-744’s role in breast cancer is unknown, but is tumor-suppressive in vitro. We hypothesize that high expression of all three miRNAs is associated with a better survival based on their known functions in breast cancer. All data was obtained from the Cancer Genome Atlas (TCGA). Expression of miRNA-18a, miRNA-205, and miRNA-744 were retrieved from the Genomic Data Commons (GDC) data portal for analyses. After miRNA-specific thresholds were derived and used to group the patients into a high or low expression group, survival data was calculated using the Cox proportional hazard model. Further subanalyses separating the patients based on receptor status and AJCC 7th edition TNM staging were similarly compared. 1052/1097 samples logged in TCGA had clinical data and miRNA-sequence datasets on the miRNAs of interest. High expression of miRNA-18a (p=0.079), miRNA-205 (p=0.034) and miRNA-744 (p=0.0135) was associated with a better survival. On subanalysis, estrogen receptor (ER), progesterone receptor (PR) positive, and lymph node negative disease had a statistically significant survival advantage with miRNA-18a, miRNA-205 and miRNA-744 high expression. By utilizing a big dataset (TCGA) with sufficient statistical power, we found that high expression of miRNA-18a, miRNA-205, and miRNA-744 in the breast tumor samples were all associated with better overall survival in ER/PR positive, lymph node negative disease supporting their role as a tumor suppressor in breast cancer.
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发表时间: 2014-07-28
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