Serum high expression of miR-214 and miR-135b as novel predictor for myeloma bone disease development and prognosis
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Mu Hao1,2, Meirong Zang1, Lei Zhao3, Shuhui Deng1, Yan Xu1, Fang Qi1, Gang An1, Yu Qin1, Weiwei Sui1, Fei Li1, Wenjuan Yang1, Zengjun Li1, Shuhua Yi1, Dehui Zou1, Fenghuang Zhan2, Lugui Qiu1
1State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin 300020, China
2Division of Hematology, Oncology, and Blood and Marrow Transplantation, Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA
3Department of Molecular Physiology and Biophysics, Holden Comprehensive Cancer Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
Mu Hao, e-mail: [email protected]
Lugui Qiu, e-mail: [email protected]
Keywords: serum miRNAs, bone disease, multiple myeloma, biomarkers
Received: September 08, 2015 Accepted: January 01, 2016 Published: February 11, 2016
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.
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