Abstract
Multiple myeloma (MM) originates from malignant plasma cells, leading to multiple destructive lytic bone lesions that occur in more than 80% of MM patients. MicroRNAs have been reported to be involved in development of bone lesions in MM. However, the circulating microRNA as diagnostic and prognostic biomarkers for bone lesions has not been elucidated yet. In this study, we identified differentially expressed miRNAs that are potentially involved in myeloma-related bone disease in serum of MM patients. MiR-214 and miR-135b was shown to be increased in serum of MM patients with bone lesions. Serum level of miR-214 and miR-135b was highly correlated with the severity of lytic bone lesions and demonstrated as a diagnostic tool for identifying bone diseases based on results of a receiver operating characteristic analysis (ROC). In addition, patients with high levels of serum miR-214 had a dismal survival with significantly shortened progression free survival (PFS) and overall survival (OS). Interestingly, bisphosphonates treatment significantly extended PFS and OS in patients with higher level of miR-214 comparing to patients without bisphosphonates treatment. Taken together, our findings revealed the significance of circulating miR-214 and miR-135b levels in detection of bone disease and in prediction of prognosis of patients with multiple myeloma, suggesting its potential clinical applications. The result of this study also set the foundation for searching more circulating miRNA as biomarker for tumor bone lesions.
Highlights
Multiple myeloma (MM) originates from clonal expansion of malignant plasma cells in bone marrow, leading to multiple destructive lytic bone lesions at the time of diagnosis [1]
We mainly focus on the potential clinical significance of circulating miRNAs as diagnostic, prognostic, and predictive biomarkers for myeloma bone disease
Useful biomarkers must combine good measurability, validated association with biological processes or outcomes, and should support clinical decision making if used in clinical practices
Summary
Multiple myeloma (MM) originates from clonal expansion of malignant plasma cells in bone marrow, leading to multiple destructive lytic bone lesions at the time of diagnosis [1]. Dysregulation of miRNAs in MM cells and bone marrow microenvironment has important impacts on the initiation and progression of myeloma bone disease [6, 7]. Compared to conventional diagnostic parameters, the circulating miRNA profile is appropriate for the diagnosis of bone disease and estimates patient progression and therapeutic outcome with higher specificity and sensitivity. The diagnostic and prognostic values of circulating miRNA in bone diseases, including myeloma bone disease have not been evaluated. We mainly focus on the potential clinical significance of circulating miRNAs as diagnostic, prognostic, and predictive biomarkers for myeloma bone disease
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