The Prognostic Role of Cyclin D1 in Multiple Myeloma: A Systematic Review and Meta-Analysis

Purpose: Cyclin D1 has been identified as a proto-oncogene associated with the uncontrolled proliferation of tumor cells. This systematic review and meta-analysis aims to estimate the prognostic significance of cyclin D1 in multiple myeloma (MM) patients. Method: We searched for qualified data in PubMed, Embase, and Web of Science up to February 2020. Data quality was assessed by the Newcastle-Ottawa scale (NOS). Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were used to evaluate the relationship between cyclin D1 expression and overall survival (OS), progression-free survival (PFS)/event-free survival (EFS) in patients with MM. Result: A total of 13 studies involving 961 patients were included. Overall, pooled analysis revealed significant heterogeneity between cyclin D1 expression and the prognosis of MM (OS, HR = 1.08, 95% CI: 0.71-1.64, I-2 = 67.9%; PFS/EFS, HR = 0.97, 95% CI: 0.49-1.93, I-2 = 85.8%). Subgroup analysis revealed that the prolongation of OS was relevant to increased expression of cyclin D1 in MM patients in the relapsed and refractory group (OS, HR = 0.46, 95% CI: 0.24-0.90). Another subgroup assessment of OS established that MM patients with CCND1 overexpression in the bortezomib group had longer survival time (HR = 0.30, 95% CI: 0.11-0.82), whereas, those overexpressing CCND1 in the conventional chemotherapy group had poor prognosis (HR = 2.19, 95% CI: 1.18-4.08). We also found that increased cyclin D1 expression correlated favorably with PFS in the autologous stem cell transplantation (ASCT) (HR = 0.45, 95% CI: 0.28-0.73) or reverse transcription-polymerase chain reaction (RT-PCR) group (HR = 0.41, 95% CI: 0.26-0.64). Conclusion: The result of this meta-analysis suggested that CCND1 overexpression might be a predictive biomarker for MM patients when treated with bortezomib, receiving ASCT, or in relapsed and refractory period.

Automated summary

This study aimed to evaluate the prognostic significance of Cyclin D1 in multiple myeloma patients. The results showed that overexpression of Cyclin D1 might be a predictive biomarker for patients treated with bortezomib, undergoing autologous stem cell transplantation, or in the relapsed and refractory period.