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一种通过上皮-间质转化(EMT)途径预测胶质瘤预后的放射敏感性基因特征。

A radiosensitivity gene signature in predicting glioma prognostic via EMT pathway.

作者信息

Meng Jin, Li Ping, Zhang Qing, Yang Zhangru, Fu Shen

机构信息

Department of Radiation Oncology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, China.

Radiation Oncology Center, Fudan University Shanghai Cancer Center (FUSCC), Shanghai, China. Radiation Oncology Dept, Shanghai Proton and Heavy Ion Center (SPHIC), Shanghai, China.

出版信息

Oncotarget. 2014 Jul 15;5(13):4683-93. doi: 10.18632/oncotarget.2088.

Abstract

A 31-gene signature derived by integrating four different microarray experiments, has been found to have a potential for predicting radiosensitivity of cancer cells, but it was seldom validated in clinical cancer samples. We proposed that the gene signature may serve as a predictive biomarker for estimating the overall survival of radiation-treated patients. The significance of gene signature was tested in two previously published datasets from Gene Expression Omnibus (GEO) and The Cancer Genome Altas (TCGA), respectively. In GEO data set, patients predicted to be radiosensitive(RS) had an improved overall survival when compared with radioresistant(RR) patients in either radiotherapy(RT)-treated or non radiotherapy(RT)-treated subgroups(p<0.0001 in the RT-treated group). Multivariate Cox regression analysis showed that the gene signature is the strongest predictor(p=0.0093) in the RT-treated subgroup of patients. However, it does not remain significant (p=0.7668) in non radiotherapy-treated group when adjusting for age and Karnofsky performance score (KPS) as covariates. Similarly, in the TCGA data set, radiotherapy-treated glioblastoma multiforme(GBM) patients assigned to RS group had an improved overall survival compared with RR group(p<0.0001). Geneset enrichment analysis(GSEA) analysis revealed that enrichment of epithelial mesenchymal transition(EMT) pathway was observed with radioresistant phenotype. These results suggest that the signature is a predictive biomarker for radiation-treated glioma patients' prognostic.

摘要

通过整合四个不同的微阵列实验得出的一个31基因特征,已被发现具有预测癌细胞放射敏感性的潜力,但在临床癌症样本中很少得到验证。我们提出该基因特征可作为一种预测性生物标志物,用于估计接受放射治疗患者的总生存期。分别在来自基因表达综合数据库(GEO)和癌症基因组图谱(TCGA)的两个先前发表的数据集中测试了基因特征的意义。在GEO数据集中,预测为放射敏感(RS)的患者,在放疗(RT)治疗组或非放疗(RT)治疗组中,与放射抵抗(RR)患者相比,总生存期均有所改善(RT治疗组p<0.0001)。多变量Cox回归分析表明,该基因特征是RT治疗患者亚组中最强的预测因子(p=0.0093)。然而,在将年龄和卡诺夫斯基功能状态评分(KPS)作为协变量进行调整时,在非放疗治疗组中它不再具有显著性(p=0.7668)。同样,在TCGA数据集中,分配到RS组的接受放疗的多形性胶质母细胞瘤(GBM)患者与RR组相比,总生存期有所改善(p<0.0001)。基因集富集分析(GSEA)显示,放射抵抗表型存在上皮-间质转化(EMT)通路的富集。这些结果表明,该特征是放射治疗的胶质瘤患者预后的预测性生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2efa/4148091/2c6d0105e80d/oncotarget-05-4683-g001.jpg

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