Expression profiling of ion channel genes predicts clinical outcome in breast cancer.
Expression profiling of ion channel genes predicts clinical outcome in breast cancer.
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DOI：
10.1186/1476-4598-12-106
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发表时间：
2013-09-22
期刊：
影响因子：
37.3
通讯作者：
Zhou T
中科院分区：
文献类型：
--
作者：
Ko JH;Ko EA;Gu W;Lim I;Bang H;Zhou T
离子通道在多种生物过程中发挥着关键作用，包括人类癌症的发展。然而，离子通道对乳腺癌致瘤性的总体影响仍存在争议。我们对280个离子通道基因进行了微阵列meta分析。我们根据基因表达谱确定与乳腺癌有关的候选离子通道。我们在发现队列中测试了离子通道基因的表达与p53突变状态、ER状态和组织学肿瘤分级之间的关系。由离子通道基因（IC30）组成的分子特征通过Spearman等级相关检验在肿瘤分级与基因表达之间确定。在IC30的基础上开发了风险评分系统。我们通过Cox比例风险回归和log-rank检验在发现队列和7个验证队列中检验IC30的预后能力。在发现队列中，22、24和30个离子通道基因在p53突变状态、ER状态和肿瘤组织学分级的变化中差异表达。我们将30个肿瘤级别相关的离子通道基因指定为IC30基因标记。我们发现IC30风险评分在发现队列和7个验证队列中的6个中预测临床结局（P < 0.05）。在两个验证队列中进行的多因素和单因素试验表明，IC30是一种可靠的预后生物标志物，不受患者年龄、淋巴结状态、肿瘤大小、肿瘤分级、雌激素和孕激素受体状态、p53突变状态等标准临床和病理预后因素的影响。我们确定了一个分子基因标记IC30，它代表了一个有希望的乳腺癌诊断和预后生物标志物。我们的研究结果表明，有关肿瘤病理中离子通道表达的信息可以为人类癌症的治疗提供新的靶点。
Ion channels play a critical role in a wide variety of biological processes, including the development of human cancer. However, the overall impact of ion channels on tumorigenicity in breast cancer remains controversial. We conduct microarray meta-analysis on 280 ion channel genes. We identify candidate ion channels that are implicated in breast cancer based on gene expression profiling. We test the relationship between the expression of ion channel genes and p53 mutation status, ER status, and histological tumor grade in the discovery cohort. A molecular signature consisting of ion channel genes (IC30) is identified by Spearman’s rank correlation test conducted between tumor grade and gene expression. A risk scoring system is developed based on IC30. We test the prognostic power of IC30 in the discovery and seven validation cohorts by both Cox proportional hazard regression and log-rank test. 22, 24, and 30 ion channel genes are found to be differentially expressed with a change in p53 mutation status, ER status, and tumor histological grade in the discovery cohort. We assign the 30 tumor grade associated ion channel genes as the IC30 gene signature. We find that IC30 risk score predicts clinical outcome (P < 0.05) in the discovery cohort and 6 out of 7 validation cohorts. Multivariate and univariate tests conducted in two validation cohorts indicate that IC30 is a robust prognostic biomarker, which is independent of standard clinical and pathological prognostic factors including patient age, lymph node status, tumor size, tumor grade, estrogen and progesterone receptor status, and p53 mutation status. We identified a molecular gene signature IC30, which represents a promising diagnostic and prognostic biomarker in breast cancer. Our results indicate that information regarding the expression of ion channels in tumor pathology could provide new targets for therapy in human cancers.
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影响因子：
3.8
作者：
Khaitan D;Sankpal UT;Weksler B;Meister EA;Romero IA;Couraud PO;Ningaraj NS
通讯作者：
Ningaraj NS
DOI：
10.1001/jama.2011.593
发表时间：
2011-05-11
期刊：
JAMA
影响因子：
--
作者：
Hatzis C;Pusztai L;Valero V;Booser DJ;Esserman L;Lluch A;Vidaurre T;Holmes F;Souchon E;Wang H;Martin M;Cotrina J;Gomez H;Hubbard R;Chacón JI;Ferrer-Lozano J;Dyer R;Buxton M;Gong Y;Wu Y;Ibrahim N;Andreopoulou E;Ueno NT;Hunt K;Yang W;Nazario A;DeMichele A;O'Shaughnessy J;Hortobagyi GN;Symmans WF
通讯作者：
Symmans WF
DOI：
10.1007/s00249-004-0389-0
发表时间：
2004-05-01
影响因子：
2
作者：
Diss, JKJ;Fraser, SP;Djamgoz, MBA
通讯作者：
Djamgoz, MBA
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
2
作者：
Haren, Nathalie;Khorsi, Hafida;Ouadid-Ahidouch, Halima
通讯作者：
Ouadid-Ahidouch, Halima