Affiliation:
1. From the Thoracic Oncology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.
Abstract
PurposeRRM1 has important functions in the determination of the malignant phenotype. It controls cell proliferation through deoxynucleotide production and metastatic propensity through PTEN induction. It is located in a region of loss of heterozygosity in non–small-cell lung cancer (NSCLC), which is a predictor of poor survival. We hypothesized that RRM1 expression would be a significant predictor of outcome in NSCLC.Patients and MethodsA retrospective data set of 49 patients and a prospective data set of 77 patients with resectable NSCLC were studied. RNA was extracted from tumor and normal lung tissue, and expression of the genes RRM1, PTEN, and RRM2 was determined by real-time quantitative polymerase chain reaction.ResultsRRM1 expression was significantly correlated with PTEN and RRM2 expression in tumor tissue. RRM1 and PTEN expression in tumor tissue was highly predictive of overall (P = .011 and .018, respectively) and disease-free survival (P = .002 and .026, respectively). Patients with high levels of expression lived longer and had disease recurrence later than patients with low levels of RRM1 and PTEN. In a multivariate analysis, high RRM1 expression was predictive of long survival independent of tumor stage, performance status, and weight loss.ConclusionRRM1 is a biologically and clinically important determinant of malignant behavior in NSCLC. Knowing the level of expression of this gene adds significant information to management decisions independent of the currently used outcome predictors of tumor stage, performance status, and weight loss. Future clinical trials should stratify patients based on expression of this gene to avoid unwanted biases.
Publisher
American Society of Clinical Oncology (ASCO)
Reference38 articles.
1. Engstroem Y, Eriksson S, Jildevik I, et al: Cell cycle-dependent expression of mammalian ribonucleotide reductase. J Biol Chem 260:9114,1985–9116,
2. Mann GJ, Musgrove EA, Fox RM, et al: Ribonucleotide reductase M1 subunit in cellular proliferation, quiescence, and differentiation. Cancer Res 48:5151,1988–5156,
3. Ribonucleotide reductase: regulation, regulation, regulation
4. The R1 component of mammalian ribonucleotide reductase has malignancy-suppressing activity as demonstrated by gene transfer experiments
5. RRM1-induced metastasis suppression through PTEN-regulated pathways
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