RESUMO
The microRNA expression profile of plasma exosomes in osteosarcoma needs to be further explored. The present study intends to investigate the practicality of plasma exosomal miRNAs as novel biomarkers of osteosarcoma. In the study, exosome-like vesicles were purified from the plasma of patients with osteosarcoma and healthy control. Differential centrifugation was used. The purified vesicles which ranged from 50 to 100 nm in size were identified as exosomes by transmission electron microscopy and western blot. Validating assays in vitro and in vivo were performed via CCK8, reverse transcription-quantitative PCR, flow cytometry, transwell and wound healing assays and xenograft model. High-throughput sequencing identified that 57 miRNAs, 20 of which were upregulated and 37 downregulated, were differentially expressed in patients with osteosarcoma and healthy control (p<0.01; fold change ≥3). In comparison to the controls, the expression levels of miR-92a-3p, miR-130a-3p, miR-195-3 p, miR-335-5 p, let-7i-3p were upregulated in the exosomes from patients with osteosarcoma with statistical significance. Studies in vitro and in vivo have proved that osteosarcoma-secreted exosomes from miR-195-3 p upregulated 143B osteosarcoma cells promote cell proliferation and invasion. Overall, the present study identified exosomal miRNAs with dysregulated expression in patients with osteosarcoma, and they may have potential as targets for the treatment of patients with osteosarcoma.
Assuntos
Exossomos/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , MicroRNAs/genética , Osteossarcoma/sangue , Osteossarcoma/genética , Animais , Linhagem Celular Tumoral , Proliferação de Células/genética , Exossomos/metabolismo , Exossomos/ultraestrutura , Ontologia Genética , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/metabolismo , Invasividade Neoplásica , Osteossarcoma/patologia , Reprodutibilidade dos Testes , Adulto JovemRESUMO
BACKGROUND: B7-H3 exhibits altered expression in various cancers. However, the correlation between B7-H3 expression and prognosis of cancer patients remains controversial. Therefore, we elicit a meta-analysis to investigate the potential value of B7-H3 in the prognostic prediction in human cancers. MATERIALS AND METHODS: We searched PubMed (last update by June 15th, 2016) to identify studies assessing the effect of B7-H3 on survival of cancer patients. Hazard ratios (HRs) for overall survival (OS), recurrence free survival (RFS) and progression-free survival (PFS) from individual studies were calculated and pooled by using a random-effect or fix-effect model, and heterogeneity and publication bias analyses were also performed. RESULTS: Data from 24 observational studies consisting of 4141 patients were summarized. An elevated baseline B7-H3 was significantly correlated with poor OS (pooled HR = 2.09; 95% CI =1.60-2.74; P < 0.001). Differences across subgroups of tumor type (P = 0.324), year of publication (P = 0.431), ethnicity (P = 0.940), source of HR (P = 0.145), analysis type (P = 0.178) and sample size (P = 0.909) were not significant. Furthermore, high B7-H3 expression also predicted a significantly poor RFS (pooled HR = 1.39; 95% CI = 1.11-1.75; P = 0.004) but not PFS. CONCLUSIONS: This meta-analysis clarifies that elevated B7-H3 expression is significantly associated with poor survival in cancer patients.
