The circadian gene NPAS2 is a novel prognostic biomarker for breast cancer.
The circadian gene NPAS2 is a novel prognostic biomarker for breast cancer.
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DOI：
10.1007/s10549-009-0484-0
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发表时间：
2010-04
影响因子：
3.8
通讯作者：
Katsaro, Dionyssios
中科院分区：
文献类型：
--
作者：
Yi, Chunhui;Mu, Lina;de la Longrais, Irene A. Rigault;Sochirca, Olga;Arisio, Riccardo;Yu, Herbert;Hoffman, Aaron E.;Zhu, Yong;Katsaro, Dionyssios
越来越多的证据表明，神经元PAS结构域蛋白2 （NPAS2）和其他昼夜节律基因可能通过控制癌症相关的生物学途径参与肿瘤的发生和生长。NPAS2的错义多态性（Ala394Thr）已被证明与包括乳腺癌在内的人类肿瘤的风险相关。本研究通过对Ala394Thr多态性进行基因分型并检测NPAS2的表达，进一步探讨了NPAS2在乳腺癌中的预后意义。从348例乳腺癌组织样本中提取DNA，采用TaqMan等位基因鉴别法分析NPAS2基因型。其中，287个还具有可用于实时PCR检测NPAS2表达的总RNA。分析NPAS2基因型和表达水平与预后结果的关系，以及与临床特征的相关性。高水平的NPAS2表达与改善无病生存（AHR = 0.43, 95% CI: 0.21-0.86， P趋势= 0.022）和总生存（AHR = 0.42, 95% CI: 0.19-0.96， P趋势= 0.036）密切相关。此外，与Thr394Thr对应的NPAS2基因型与无病生存之间存在临界但不显著的相关性（AHR = 1.82, 95% CI: 0.96-3.46）。Ala/Ala、Ala/Thr和Thr/Thr基因型在肿瘤严重程度上也存在差异（χ2 (6df, N = 344) = 14.96, P = 0.020）。这些发现提供了第一个证据，表明昼夜节律基因NPAS2在乳腺癌中的预后意义。
Mounting evidence suggests that neuronal PAS domain protein 2 (NPAS2) and other circadian genes are involved in tumorigenesis and tumor growth, possibly through their control of cancer-related biologic pathways. A missense polymorphism in NPAS2 (Ala394Thr) has been shown to be associated with risk of human tumors including breast cancer. The current study further examined the prognostic significance of NPAS2 in breast cancer by genotyping the Ala394Thr polymorphism and measuring NPAS2 expression. DNA extracted from 348 breast cancer tissue samples was analyzed for NPAS2 genotype using the TaqMan allelic discrimination assay. Of these, 287 also had total RNA available for use in real-time PCR assays to determine NPAS2 expression. NPAS2 genotypes and expression levels were analyzed for associations with prognostic outcomes, as well as correlations with clinical characteristics. A high level of NPAS2 expression was strongly associated with improved disease free survival (AHR = 0.43, 95% CI: 0.21–0.86, P trend = 0.022) and overall survival (AHR = 0.42, 95% CI: 0.19–0.96, P trend = 0.036). In addition, there was a borderline, but nonsignificant association between the NPAS2 genotype corresponding to Thr394Thr and disease free survival (AHR = 1.82, 95% CI: 0.96–3.46). The Ala/Ala, Ala/Thr, and Thr/Thr genotypes were also differentially distributed by tumor severity, as measured by TNM classification (χ2 (6df, N = 344) = 14.96, P = 0.020). These findings provide the first evidence suggesting prognostic significance of the circadian gene NPAS2 in breast cancer.
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