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Serum high expression of miR-214 and miR-135b as novel predictor for myeloma bone disease development and prognosis

2016; Impact Journals LLC; Volume: 7; Issue: 15 Linguagem: Inglês

10.18632/oncotarget.7319

1949-2553

Mu Hao, Meirong Zang, Lei Zhao, Shuhui Deng, Yan Xu, Qi Fang, Gang An, Yu Qin, Weiwei Sui, Fei Li, Wenjuan Yang, Zengjun Li, Shuhua Yi, Dehui Zou, Fenghuang Zhan, Lugui Qiu,

Peptidase Inhibition and Analysis

// Mu Hao 1, 2 , Meirong Zang 1 , Lei Zhao 3 , Shuhui Deng 1 , Yan Xu 1 , Fang Qi 1 , Gang An 1 , Yu Qin 1 , Weiwei Sui 1 , Fei Li 1 , Wenjuan Yang 1 , Zengjun Li 1 , Shuhua Yi 1 , Dehui Zou 1 , Fenghuang Zhan 2 , Lugui Qiu 1 1 State 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 2 Division of Hematology, Oncology, and Blood and Marrow Transplantation, Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA 3 Department of Molecular Physiology and Biophysics, Holden Comprehensive Cancer Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA Correspondence to: Mu Hao, e-mail: haomusg@163.com Lugui Qiu, e-mail: drqiu99@medmail.com.cn Keywords: serum miRNAs, bone disease, multiple myeloma, biomarkers Received: September 08, 2015 Accepted: January 01, 2016 Published: February 11, 2016 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.