Comprehensive expression analysis of retinoic acid receptors and retinoid X receptors in non-small cell lung cancer:: implications for tumor development and prognosis
Comprehensive expression analysis of retinoic acid receptors and retinoid X receptors in non-small cell lung cancer:: implications for tumor development and prognosis
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DOI：
10.1093/carcin/bgi006
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发表时间：
2005-03-01
期刊：
影响因子：
4.7
通讯作者：
Schneider, PM
中科院分区：
文献类型：
--
作者：
Brabender, J;Metzger, R;Schneider, PM
视黄酸受体（RAR）和类视黄醇X受体（RXR）在调节细胞的发育、生长和分化中发挥重要作用，并对非小细胞肺癌（NSCLC）细胞的生长具有抑制作用。目前缺乏对大量 NSCLC 患者中所有 RAR 和 RXR 亚型 mRNA 表达及其在该疾病发生和进展中的作用的综合分析。使用实时定量 RT-PCR 方法，我们分析了 88 例 NSCLC 患者的肿瘤和匹配的正常组织中所有视黄醇受体亚型的 mRNA 表达。检测肿瘤组织中的基因表达频率如下：RARα 100%、RARbeta 94%、RARgamma 94%、RXRα 100%、RXRbeta 100%和RXRgamma 92%。与匹配的正常组织相比，肿瘤组织中的 mRNA 表达水平相等或降低，频率如下：RARalpha 76.1%、RARbeta 59.1%、RARgamma 39.8%、RXRalpha 67.1%、RXRbeta 54.5% 和 RXRgamma 88.6%，并且与任何一种其他亚型显着相关。没有或任何两种亚型、任何三种或四种亚型或任何五种或六种亚型低基因表达的患者之间的生存概率存在显着差异（P = 0.004，对数秩检验）。多变量分析证实低基因表达状态是一个显着的独立不利预后因素（P = 0.015）。我们的结果表明，所有 RAR 和 RXR 受体亚型的表达降低是 NSCLC 中的常见事件。所有类视黄醇亚类表达的广泛共同调节下调表明这种癌症中类视黄醇通路的根本失调。肿瘤组织中 RAR 和 RXR mRNA 表达水平的定量是 NSCLC 化学预防试验的候选预后标志物和替代生物标志物。
Retinoic acid receptors (RARs) and retinoid X receptors (RXRs) are important in regulating the development, growth and differentiation of cells and have inhibitory effects on non-small cell lung cancer (NSCLC) cell growth. A comprehensive analysis of all RAR and RXR subtypes mRNA expression in a large series of patients with NSCLC and their role in the development and progression of this disease is lacking. Using a quantitative real-time RT-PCR method, we analyzed the mRNA expression of all retinoid receptor subtypes in tumor and matching normal-appearing tissues of 88 patients with NSCLC. Gene expression in tumor tissues was detected with the following frequencies: RARalpha 100%, RARbeta 94%, RARgamma 94%, RXRalpha 100%, RXRbeta 100% and RXRgamma 92%. Levels of mRNA expression in tumor tissues compared with matching normal-appearing tissue were equal or reduced with the following frequencies: RARalpha 76.1%, RARbeta 59.1%, RARgamma 39.8%, RXRalpha 67.1%, RXRbeta 54.5% and RXRgamma 88.6%, and were significantly associated with any one other subtype. The probability of survival was significantly different among patients with low gene expression in no or any two subtypes, any three or four subtypes or any five or six subtypes (P = 0.004, log rank test). Multivariate analysis confirmed low gene expression status as a significant independent unfavorable prognostic factor (P = 0.015). Our results show that decreased expression of all RAR and RXR receptor subtypes is a frequent event in NSCLC. Widely co-regulated down-regulation of expression of all retinoid subclasses suggests a fundamental dysregulation of the retinoid pathway in this cancer. Quantitation of RAR and RXR mRNA expression levels in tumor tissue is a candidate prognostic marker and surrogate biomarker for chemopreventive trials in NSCLC.