RESUMO
OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Assuntos
Neoplasias Ósseas/genética , Tumor de Células Gigantes do Osso/genética , MicroRNAs/biossíntese , MicroRNAs/genética , RNA Neoplásico , Adolescente , Adulto , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Neoplasias Ósseas/metabolismo , Feminino , Tumor de Células Gigantes do Osso/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Osteoclastos , Estudos Retrospectivos , Adulto JovemRESUMO
The aim of the present study was to evaluate the influence of polymorphisms in NER and HRR pathways on the response to cisplatin-based treatment and clinical outcome in osteosarcoma patients. 214 osteosarcoma patients treated with cisplatin-based chemotherapy were collected between January 2008 and January 2011. Genotypes of ERCC1 rs11615, ERCC2 rs1799793 and rs13181, NBN rs709816, RAD51 rs1801320, and XRCC3 rs861539 were conducted by Polymerase Chain Reaction Restriction Fragment Length Polymorphism (PCR-RFLP) assay. By conditional logistic regression analysis, patients carrying CC genotype of ERCC1 rs11615 showed a significant more good responder than TT genotype, and the OR (95% CI) was 2.51 (1.02-6.85). In the Cox proportional hazards model, after adjusting for potential confounding factors, we found that individuals carrying CC genotype of ERCC1 rs11615 was associated with decreased risk of death from osteosarcoma, and the HR (95% CI) was 0.43 (0.15-0.93). In conclusion, our results suggest that ERCC1 rs11615 polymorphism in the DNA repair pathways play an important role in the response to chemotherapy and overall survival of osteosarcoma.
Assuntos
Neoplasias Ósseas/genética , Reparo do DNA/genética , Resistencia a Medicamentos Antineoplásicos/genética , Osteossarcoma/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/mortalidade , Proteínas de Ciclo Celular/genética , Criança , Proteínas de Ligação a DNA/genética , Endonucleases/genética , Feminino , Genótipo , Humanos , Estimativa de Kaplan-Meier , Masculino , Proteínas Nucleares/genética , Osteossarcoma/tratamento farmacológico , Osteossarcoma/mortalidade , Polimorfismo de Fragmento de Restrição , Modelos de Riscos Proporcionais , Rad51 Recombinase/genética , Proteína Grupo D do Xeroderma Pigmentoso/genética , Adulto JovemRESUMO
The association between TGF-ß1 +869C/T polymorphism and risk of fractures remained controversial. Therefore, we performed this meta-analysis to investigate this association. We searched PubMed, EMBASE, and Wangfang databases for studies before Aug 2014. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to calculate the strength of association. A total of ten studies were included in this meta-analysis. TGF-ß1 +869C/T polymorphism was associated with a significantly increased risk of fracture (OR=1.41; 95% CI, 1.20-1.65; I(2) =0%). In the subgroup analysis according to gender, women was significantly associated with risk of fracture (OR=1.44; 95% CI, 1.20-1.73; I(2) =4%). In the subgroup analysis by race, Asians (OR=1.43; 95% CI, 1.06-1.92; I(2) =0%) and Caucasians (OR=1.44; 95% CI, 1.13-1.85; I(2) =15%) showed increased fracture risk. Our meta-analysis suggested that the TGF-ß1 +869C/T polymorphism may be a risk factor for developing fracture.