Carcinogenesis Advance Access published online on December 23, 2004
Carcinogenesis, doi:10.1093/carcin/bgi006
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1 Department of Visceral- and Vascular Surgery, University of Cologne, 50931 Germany
* To whom correspondence should be addressed. Background: Retinoic acid receptors (RARs) and retinoid X receptors (RXRs) are important for 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 RARs and RXRs subtypes mRNA expression in a large series of patients with NSCLC and their role in the development and progression of this disease is lacking. Methods: 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. Results: Gene expression in tumor tissues was detected with the following frequencies: RAR Conclusion: Our results show that decreased expression of all RAR and RXR receptor subtypes is a frequent event in NSCLC. Widely coregulated downregulation 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.
Received June 3, 2004
Revised November 20, 2004
Accepted December 15, 2004
CANCER BIOLOGY
Comprehensive expression analysis of retinoc acid receptors and retinoid X receptors in non-small cell lung cancer: implications for tumor development and prognosis
2 Response Genetics Inc., Los Angeles, CA 90033, USA
3 Department of Biochemistry and Molecular Biology, University of Southern California Keck School of Medicine and USC/Kenneth Norris Comprehensive Cancer Center, Los Angeles, CA 90033, USA
Jan Brabender, E-mail: jan.brabender{at}t-online.de
Abstract 
100%, RAR
94%, RAR
94%, RXR 100%, RXR 100%, and RXR 92%. Levels of mRNA expression in tumor tissues compared to matching normal appearing tissue were equal or reduced with the following frequencies: RAR 76.1%, RAR 59.1%, RAR 39.8%, RXR 67.1%, RXR 54.5%, RXR 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 (LG0/2), any 3 or 4 subtypes (LG3/4) or any 5 or 6 subtypes (LG5/6). (P=0.004, log-rank test). Multivariate analysis confirmed LG status as a significant independent unfavorable prognostic factor (P=0.015).
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