Expression of cyclin D1 splice variants is differentially associated with outcome in non-small cell lung cancer patients

Real-time reverse transcription polymerase chain reaction and immunohistochemistry were used to evaluate the messenger RNA (mRNA) and protein expression levels of total cyclin D1 and its splice variants (cyclin D1a and cyclin D1b) in 102 paired malignant and nonmalignant tissues from patients with non-small cell lung cancer, respectively. The expression levels of total cyclin D1 and its splice variants were significantly up-regulated in malignant tissues than in nonmalignant tissues at both mRNA and protein levels. Although the expression levels of cyclin D I a were higher than those of cyclin D1b, the relative expression ratios of cyclin DIb mRNA between malignant and nonmalignant lung tissues were obviously higher than those of cyclin D I a mRNA. Analysis of variance showed that cyclin DIb rnRNA expression was significantly associated with the histologic grade, lymph node metastasis, distant metastasis, and tumor stage of patients, whereas cyclin D I a mRNA expression was not related to clinicopathologic characteristics except sex. Patients with cyclin DIb mRNA expression above the median value had shorter survival than those below the median value (P =.033). Similarly, cyclin DIb immunopositivity was also associated with histologic grade, and patients with immunostaining positivity for cyclin D1b showed poor survival (P =.005). Multivariate analysis demonstrated that cyclin DIb immunopositivity was an independent risk factor in survival of patients with non-small cell lung cancer (P =.018). Our data show that cyclin DIb, rather than canonical cyclin D1a, might contribute to the development of non-small cell lung cancer. Cyclin D I b would be a better prognostic indicator for non-small cell lung cancer as compared to total cyclin D1 or cyclin D1a. (C) 2009 Elsevier Inc. All rights reserved.