A novel five gene signature derived from stem-like side population cells predicts overall and recurrence-free survival in NSCLC.
A novel five gene signature derived from stem-like side population cells predicts overall and recurrence-free survival in NSCLC.
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DOI：
10.1371/journal.pone.0043589
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Chellappan SP
中科院分区：
文献类型：
--
作者：
Perumal D;Singh S;Yoder SJ;Bloom GC;Chellappan SP
基因表达谱已被用来表征各种癌症的预后。早期的研究表明，从非小细胞肺癌（NSCLC）细胞系中分离的侧群细胞表现出癌症干细胞的特性。在这项研究中，我们将系统生物学方法应用于从肺癌细胞系中分离的癌干细胞样细胞的基因表达谱数据，以确定可以预测预后的新基因特征。从4个NSCLC细胞系（A549, H1650, H460, H1975）分离的侧群（SP）和主群（MP）细胞的微阵列数据检测了与茎样性状相关的基因表达谱。差异表达基因在所有4个细胞系中普遍存在至少2倍的过表达或过表达。我们发现与MP细胞相比，SP细胞中354个表达上调，126个表达下调；其中，89个上调基因和62个下调基因（平均2倍变化）用于主成分分析（PCA）和MetaCore™途径分析。途径分析表明，在染色体凝聚途径中有4个上调基因（TOP2A、AURKB、BRRN1、CDK1），在染色体易位中有1个下调基因FUS。采用qRT-PCR对所选的5个基因进行微阵列数据验证，结果表明微阵列与qRT-PCR之间存在显著相关性。此外，我们分析了两个独立的基因表达数据集，其中包括来自NCI主任挑战集的360例肺腺癌患者的总生存率和来自成均馆大学（SKKU）的63例无复发生存率。Kaplan-Meier和log-rank检验分析预测两组数据的患者生存率均较低。我们的研究结果表明，参与染色体凝聚的基因可能与茎样特性有关，并可能预测肺腺癌的生存。我们的研究结果强调了一个基因标记，可以有效地识别预后不良的肺腺癌患者，并为这类患者设计更积极的治疗方法。
Gene expression profiling has been used to characterize prognosis in various cancers. Earlier studies had shown that side population cells isolated from Non-Small Cell Lung Cancer (NSCLC) cell lines exhibit cancer stem cell properties. In this study we apply a systems biology approach to gene expression profiling data from cancer stem like cells isolated from lung cancer cell lines to identify novel gene signatures that could predict prognosis. Microarray data from side population (SP) and main population (MP) cells isolated from 4 NSCLC lines (A549, H1650, H460, H1975) were used to examine gene expression profiles associated with stem like properties. Differentially expressed genes that were over or under-expressed at least two fold commonly in all 4 cell lines were identified. We found 354 were upregulated and 126 were downregulated in SP cells compared to MP cells; of these, 89 up and 62 downregulated genes (average 2 fold changes) were used for Principle Component Analysis (PCA) and MetaCore™ pathway analysis. The pathway analysis demonstrated representation of 4 up regulated genes (TOP2A, AURKB, BRRN1, CDK1) in chromosome condensation pathway and 1 down regulated gene FUS in chromosomal translocation. Microarray data was validated using qRT-PCR on the 5 selected genes and all showed robust correlation between microarray and qRT-PCR. Further, we analyzed two independent gene expression datasets that included 360 lung adenocarcinoma patients from NCI Director's Challenge Set for overall survival and 63 samples from Sungkyunkwan University (SKKU) for recurrence free survival. Kaplan-Meier and log-rank test analysis predicted poor survival of patients in both data sets. Our results suggest that genes involved in chromosome condensation are likely related with stem-like properties and might predict survival in lung adenocarcinoma. Our findings highlight a gene signature for effective identification of lung adenocarcinoma patients with poor prognosis and designing more aggressive therapies for such patients.
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人类TPX2是将极光-A激酶靶向纺锤体所必需的。
影响因子：
7.8
作者：
Kufer, Thomas A;Sillje, Herman H W;Korner, Roman;Gruss, Oliver J;Meraldi, Patrick;Nigg, Erich A
通讯作者：
Nigg, Erich A
影响因子：
45.3
作者：
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通讯作者：
Mitsudomi, T
DOI：
10.1016/j.bbadis.2009.02.003
发表时间：
2009-04-01
影响因子：
6.2
作者：
Lafferty-Whyte, Kyle;Cairney, Claire J.;Keith, W. Nicol
通讯作者：
Keith, W. Nicol
影响因子：
4.3
作者：
Fatoba, Samuel T.;Okorokov, Andrei L.
通讯作者：
Okorokov, Andrei L.
影响因子：
82.9
作者：
Beer, DG;Kardia, SLR;Hanash, S
通讯作者：
Hanash, S