Interactions of miR-323/miR-326/miR-329 and miR-130a/miR-155/miR-210 as prognostic indicators for clinical outcome of glioblastoma patients.
Interactions of miR-323/miR-326/miR-329 and miR-130a/miR-155/miR-210 as prognostic indicators for clinical outcome of glioblastoma patients.
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miR-323/miR-326/miR-329 和 miR-130a/miR-155/miR-210 的相互作用作为胶质母细胞瘤患者临床结果的预后指标
DOI：
10.1186/1479-5876-11-10
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发表时间：
2013-01-09
影响因子：
7.4
通讯作者：
Peng Y
中科院分区：
文献类型：
--
作者：
Qiu S;Lin S;Hu D;Feng Y;Tan Y;Peng Y
多形性胶质母细胞瘤（GBM）是最常见和最具侵袭性的脑肿瘤，临床结局较差。发现和开发新的标志物有助于GBM患者的诊断和预后。微RNA（miRNAs或miRs）的失调参与GBM。因此，我们试图鉴定和开发特异性miRNA作为GBM患者生存的预后和预测标志物。下载来自癌症基因组图谱（TCGA）数据集的480个GBM样本的miRNA和基因的表达谱以及相应的临床信息，并鉴定感兴趣的miRNA。通过Kaplan-Meier生存分析进行与感兴趣的miRNA和miRNA相互作用相关的患者总生存期（OS）和无进展生存期（PFS）。采用考克斯比例风险回归模型评价miRNA表达及相互作用对生存率的影响。利用生物信息学方法分析miRNAs的生物学过程和网络。在这项研究中，鉴定了6个感兴趣的miRNAs。生存分析显示，高水平的miR-326/miR-130a和低水平的miR-323/miR-329/miR-155/miR-210与GBM患者的OS延长显著相关，高水平的miR-326/miR-130a和低水平的miR-155/miR-210与PFS延长相关。此外，发现miRNA-323和miRNA-329在无复发或进展时间长（TTP）的患者中增加。更值得注意的是，我们的分析显示，miRNA相互作用在区分和预测OS和PFS方面更具特异性和准确性。这种相互作用更详细地分层了与不同miRNA水平相关的OS和PFS，并且与单一miRNA相比，可以获得更长的平均生存期。此外，miR-326、miR-130 a、miR-155、miR-210和4种miRNA相互作用首次被考克斯回归模型证实为生存的独立预测因子，并与临床病理因素：年龄、性别和复发一起。此外，通过网络分析、生物学过程分析、KEGG通路分析以及与基因标记的相关性分析，进一步支持了miRNA相互作用作为生存预测因子的有效性和合理性。我们的研究结果表明，miR-326，miR-130a，miR-155，miR-210和4种miRNA相互作用可以作为GBM患者生存的预后和预测标志物，这表明在改善预后工具和治疗方面具有潜在的应用价值。
Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor with poor clinical outcome. Identification and development of new markers could be beneficial for the diagnosis and prognosis of GBM patients. Deregulation of microRNAs (miRNAs or miRs) is involved in GBM. Therefore, we attempted to identify and develop specific miRNAs as prognostic and predictive markers for GBM patient survival. Expression profiles of miRNAs and genes and the corresponding clinical information of 480 GBM samples from The Cancer Genome Atlas (TCGA) dataset were downloaded and interested miRNAs were identified. Patients’ overall survival (OS) and progression-free survival (PFS) associated with interested miRNAs and miRNA-interactions were performed by Kaplan-Meier survival analysis. The impacts of miRNA expressions and miRNA-interactions on survival were evaluated by Cox proportional hazard regression model. Biological processes and network of putative and validated targets of miRNAs were analyzed by bioinformatics. In this study, 6 interested miRNAs were identified. Survival analysis showed that high levels of miR-326/miR-130a and low levels of miR-323/miR-329/miR-155/miR-210 were significantly associated with long OS of GBM patients, and also showed that high miR-326/miR-130a and low miR-155/miR-210 were related with extended PFS. Moreover, miRNA-323 and miRNA-329 were found to be increased in patients with no-recurrence or long time to progression (TTP). More notably, our analysis revealed miRNA-interactions were more specific and accurate to discriminate and predict OS and PFS. This interaction stratified OS and PFS related with different miRNA levels more detailed, and could obtain longer span of mean survival in comparison to that of one single miRNA. Moreover, miR-326, miR-130a, miR-155, miR-210 and 4 miRNA-interactions were confirmed for the first time as independent predictors for survival by Cox regression model together with clinicopathological factors: Age, Gender and Recurrence. Plus, the availability and rationality of the miRNA-interaction as predictors for survival were further supported by analysis of network, biological processes, KEGG pathway and correlation analysis with gene markers. Our results demonstrates that miR-326, miR-130a, miR-155, miR-210 and the 4 miRNA-interactions could serve as prognostic and predictive markers for survival of GBM patients, suggesting a potential application in improvement of prognostic tools and treatments.
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影响因子：
64.8
作者：
Lu, J;Getz, G;Golub, TR
通讯作者：
Golub, TR
影响因子：
11.2
作者：
Bader AG;Brown D;Winkler M
通讯作者：
Winkler M
影响因子：
2.6
作者：
Camara-Quintana, Joaquin Q.;Nitta, Ryan T.;Li, Gordon
通讯作者：
Li, Gordon
DOI：
10.1126/science.1164382
发表时间：
2008-09-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Parsons DW;Jones S;Zhang X;Lin JC;Leary RJ;Angenendt P;Mankoo P;Carter H;Siu IM;Gallia GL;Olivi A;McLendon R;Rasheed BA;Keir S;Nikolskaya T;Nikolsky Y;Busam DA;Tekleab H;Diaz LA Jr;Hartigan J;Smith DR;Strausberg RL;Marie SK;Shinjo SM;Yan H;Riggins GJ;Bigner DD;Karchin R;Papadopoulos N;Parmigiani G;Vogelstein B;Velculescu VE;Kinzler KW
通讯作者：
Kinzler KW
DOI：
10.1523/jneurosci.4966-09.2009
发表时间：
2009-12-02
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Kefas B;Comeau L;Floyd DH;Seleverstov O;Godlewski J;Schmittgen T;Jiang J;diPierro CG;Li Y;Chiocca EA;Lee J;Fine H;Abounader R;Lawler S;Purow B
通讯作者：
Purow B