The role of retinoid X receptor messenger RNA expression in curatively resected non-small cell lung cancer.
BACKGROUND
Retinoid X receptors (RXRs) have inhibitory effects on non-small cell lung cancer (NSCLC) cell growth, and RXRbeta expression is reduced in NSCLC specimens compared with normal lung tissue. We hypothesized that suppressed RXR expression might be a prognostic factor of worse clinical outcome in patients with NSCLC.


METHODS
Using a quantitative real-time reverse transcription-PCR (TaqMan) method, we analyzed RXRalpha, RXRbeta, and RXRgamma mRNA expression in normal lung tissue and matching tumor samples from 88 patients with NSCLC.


RESULTS
The median mRNA expression levels of all three RXR subtypes were frequently decreased in tumor tissues compared with matching normal lung tissue (RXRalpha, 67%; RXRbeta, 55%; RXRgamma, 89%). The RXRalpha(P = 0.001) and RXRgamma(P < 0.001) median expression levels were significantly lower in the tumors. Patients whose tumors exhibited low RXRbeta expression levels had a statistically significant worse overall survival (P = 0.0005), whereas a trend toward worse survival was observed for patients with low RXRalpha expression. Multivariate analysis indicated that low RXRbeta expression is an independent predictor of worse survival in patients with NSCLC (P = 0.017).


CONCLUSIONS
Suppressed mRNA expression of all three RXR subtypes is a frequent event in NSCLC. Reduced RXRbeta expression might be an important biomarker for more aggressive disease in patients with NSCLC.
Brabender
Jan
J
Department of Molecular Biology and Biochemistry, Norris Comprehensive Cancer Center, University of Southern California/Keck School of Medicine, Los Angeles, CA 90033, USA.
Danenberg
Kathleen D
KD
Metzger
Ralf
R
Schneider
Paul M
PM
Lord
Reginald V
RV
Groshen
Susan
S
Tsao-Wei
Denice D
DD
Park
JiMin
J
Salonga
Dennis
D
Hölscher
Arnulf H
AH
Danenberg
Peter V
PV
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000378:metabolism* / Q000601:surgery; D002470:Cell Survival; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D017434:Protein Structure, Tertiary; D012313:RNA / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000502:physiology*; D047488:Retinoid X Receptors; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014157:Transcription Factors / Q000502:physiology*; D016896:Treatment Outcome
D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; D012313:RNA