Characterization of MicroRNA Expression Profiles in Patients with Giant Cell Tumor

Giant cell tumors of bone (GCTs) are bone destructive neoplasms, the bone resorption being mediated by osteoclasts. Given that microRNAs are crucially involved in tumorigenesis and the modulation of cell fate and behavior, they are promising candidates for regulation of osteoclastogenesis. However, no reliable miRNAs profile for GCT is available. Our study aimed to evaluate osteoclastogenesis-related miRNA expression in GCTs of Chinese patients.

From January 2013 to December 2014, 11 patients with GCTs were treated in our department and grouped into a GCT group. A control group comprising four patients with benign tumors of the iliac bone was established. The diagnoses were initially established by imaging examinations and intraoperative frozen sections and later confirmed by standard histologic examination. The GCT group (five male and six female patients) were aged from 17 to 61 years (mean, 32.9 years; SD, 12.8 years). Six patients with GCT underwent intralesional curettage surgery and the other five wide resection. According to Campanacci grading, four patients had Grade I tumors, three Grade II, and three Grade III. The average age of the control group was 28.75 years (SD, 14.24 years); all of them were diagnosed as having benign tumors and underwent iliac grafting. The morphology of the excised tissue was evaluated by examining standardized hematoxylin and eosin (HE) stained paraffin-embedded samples. In all, three osteoclastogenesis-related RNAs and 20 microRNAs (miRNAs) were extracted from the patients. The strength of expression was assessed by quantitative reverse transcription polymerase chain reaction (PCR ) and the results assessed by a Student's t test.

Examination of HE stained sections revealed that the higher the Campanacci grade, the more numerous and bigger the osteoclasts (P < 0.05). PCR results indicated large amounts of osteoclast-related mRNA (cathepsin K, tartrate-resistant acid phosphatase and matrix metalloproteinase9) in GCTs (P < 0.05). Expression of six miRNAs was significantly weaker in the GCT than the control group (P < 0.05). The expression of has-mir-16-5p and has-let-7a-5p was correlated with Campanacci grade in the GCT patients (P = 0.009 and 0.034, respectively). The expression of these two miRNAs may indicate severity of bone destruction.

Overall, the clinical utility of six novel miRNA markers for GCTs was demonstrated. Of these, strength of expression of hsa-mir-16-5p and hsa-let-7a-5p may indicate the grade of bone resorption.