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全基因组 microRNA 表达谱分析鉴定出 5 个 microRNA 特征作为中国多形性胶质母细胞瘤患者的预后生物标志物。

Whole-genome microRNA expression profiling identifies a 5-microRNA signature as a prognostic biomarker in Chinese patients with primary glioblastoma multiforme.

机构信息

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

出版信息

Cancer. 2013 Feb 15;119(4):814-24. doi: 10.1002/cncr.27826. Epub 2012 Sep 18.

Abstract

BACKGROUND

More reliable clinical outcome prediction is required to better guide more personalized treatment for patients with primary glioblastoma multiforme (GBM). The objective of this study was to identify a microRNA expression signature to improve outcome prediction for patients with primary GBM.

METHODS

A cohort of Chinese patients with primary GBM (n = 82) was analyzed using whole-genome microRNA expression profiling with patients divided into a training set and a testing set. Cox regression and risk-score analyses were used to develop a 5-microRNA signature using 41 training samples. The signature was validated in 41 other test samples, in an independent cohort of 35 patients with GBM, and in the Cancer Genome Atlas data set.

RESULTS

Patients who had high risk scores according to the 5-microRNA signature had poor overall survival and progression-free survival compared with patients who had low risk scores. Multivariate Cox analysis indicated that the 5-microRNA signature was an independent prognostic biomarker after adjusting for other clinicopathologic and genetic factors, such as extent of resection, temozolomide chemotherapy, preoperative Karnofsky performance status score, isocitrate dehydrogenase 1 (IDH1) mutation, and O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status.

CONCLUSIONS

The 5-microRNA signature was identified as an independent risk predictor that identified patients who had a high risk of unfavorable outcome, demonstrating its potential for personalizing cancer management. The authors concluded that this signature should be evaluated in further prospective studies.

摘要

背景

为了更好地指导原发性多形性胶质母细胞瘤(GBM)患者的个体化治疗,需要更可靠的临床预后预测。本研究旨在确定一个 miRNA 表达谱,以改善原发性 GBM 患者的预后预测。

方法

采用全基因组 miRNA 表达谱分析对 82 例中国原发性 GBM 患者进行分析,将患者分为训练集和测试集。使用 Cox 回归和风险评分分析,从 41 个训练样本中建立一个 5-microRNA 特征。在另外 41 个测试样本、35 例 GBM 患者的独立队列和癌症基因组图谱(TCGA)数据集中对该特征进行验证。

结果

根据 5-microRNA 特征,风险评分高的患者与风险评分低的患者相比,总生存期和无进展生存期较差。多变量 Cox 分析表明,在调整其他临床病理和遗传因素(如切除范围、替莫唑胺化疗、术前卡诺夫斯基表现状态评分、异柠檬酸脱氢酶 1(IDH1)突变和 O-6-甲基鸟嘌呤-DNA 甲基转移酶(MGMT)启动子甲基化状态)后,5-microRNA 特征是独立的预后生物标志物。

结论

该 5-microRNA 特征被确定为独立的风险预测因子,可以识别出预后不良风险较高的患者,表明其在癌症管理个体化方面具有潜力。作者总结说,该特征应在进一步的前瞻性研究中进行评估。

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