No abstract

Matrix metalloproteinase 9 (MMP-9) plays an important role in the progression of several types of cancer by increasing tumor growth, migration, invasion, and metastasis and is associated with poor disease prognosis. The possible prognostic value of MMP-9 in osteosarcoma has also been examined, but due to inconsistent results between studies, it has not been possible to draw firm conclusions. To clarify this issue, we conducted a meta-analysis of published studies to provide a comprehensive evaluation of the effect of high MMP-9 expression on the survival outcomes of osteosarcoma patients. Seven studies with a total of 339 patients with osteosarcoma were examined. The pooled odds ratio (OR) with corresponding 95 % confidence interval (95 % CI) was calculated to evaluate the effect of MMP-9 expression on overall survival. Meta-analysis showed that patients with high MMP-9 expression were significantly associated with lower overall survival when compared to their counterparts with low or undetectable MMP-9 expression (OR=6.13, 95 % CI 3.45-10.89, P<0.001). Sensitivity analysis suggested the pooled OR was stable and not significantly changed when a single study was removed. The results from the systematic review and meta-analysis show that MMP-9 is an effective biomarker for predicting survival of patients with osteosarcoma.

Osteosarcoma, the most common primary bone malignancy, is characterized by easily relapsing and metastasizing. Hypoxia-inducible factor-1 (HIF-1) plays an essential role in tumorigenesis, affecting tumor metabolism, differentiation, angiogenesis, proliferation and metastasis, and has been found to be associated with survival in patients with osteosarcoma. The possible prognostic value of HIF-1 was investigated in many studies, but the results were inconsistent. We therefore conducted a meta-analysis to elucidate the correlation of HIF-1 expression, analyzed by immunohistochemistry in osteosarcoma tissues, with prognosis. The association degree was assessed by calculation of the hazard ratio (HR) and risk ratio (RR) with corresponding 95% confidence intervals (CIs). Follow-up information was available for 486 patients from 7 studies. The results showed that high HIF-1 expression was associated with a worse prognosis when compared to low or undetectable HIF-1 expression, with an HR of 3.67 (95% CI 2.24-5.99; p<0.001) for overall survival (OS) and an RR of 3.72 (95% CI 2.26-6.13; p<0.001) for OS. The RR of 2.55 for disease-free survival (DFS) did not show any obvious relationship between a high level of HIF-1 and DFS (95% CI 0.95-6.87; p = 0.064). The stability of this result was tested by sensitivity analysis and no significant change was detected. This meta-analysis suggests that HIF-1 is an effective prognostic biomarker to predict OS in patients with osteosarcoma.

Abstract. MicroRNAs (miRNAs) are a family of small non-protein coding RNAs, which regulate the expression of a wide variety of genes at the post-transcriptional level to control numerous biological and pathological processes. Various circulating miRNAs have been identified as potential diagnostic and prognostic biomarkers in multiple types of cancer and disease. The aim of the present study was to identify potential miRNA biomarkers for the early diagnosis and relapse prediction of osteosarcoma (OS). miRNA profiling was performed on serum from patients with osteosarcoma and healthy controls. All putative miRNAs were verified by reverse transcription-quantitative polymerase chain reaction analysis of 20 pre-therapeutic OS patients and 20 healthy individuals. The expression of miR-106a-5p, miR16-5p, miR-20a-5p, miR-425-5p, miR451a, miR-25-3p and miR139-5p was demonstrated to be downregulated in the serum of OS patients when compared with that of the healthy controls. Receiver-operating characteristic curve analyses indicated that these 7 miRNAs may be used as diagnostic biomarkers with the ability to discriminate between the healthy cohort and patients with OS. These results provide novel insights into the use of miRNAs in early blood screening for OS.

Objective: The aim of this study was to screen for possible biomarkers of metastatic osteosarcoma (OS) using a DNA microarray. Methods: We downloaded the gene expression profile GSE49003 from Gene Expression Omnibus database, which included 6 gene chips from metastatic and 6 from non-metastatic OS patients. The R package was used to screen and identify differentially expressed genes (DEGs) between metastatic and non-metastatic OS patients. Then we compared the expression of DEGs in the two groups and sub-grouped into up-regulated and down-regulated, followed by functional enrichment analysis using the DAVID system. Subsequently, we constructed an miRNA-DEG regulatory network with the help of WebGestalt software. Results: A total of 323 DEGs, including 134 up-regulated and 189 down-regulated, were screened out. The up-regulated DEGs were enriched in 14 subcategories and most significantly in cytoskeleton organization, while the down-regulated DEGs were prevalent in 13 subcategories, especially wound healing. In addition, we identified two important miRNAs (miR-202 and miR-9) pivotal for OS metastasis, and their relevant genes, CALD1 and STX1A. Conclusions: MiR-202 and miR-9 are potential key factors affecting the metastasis of OS and CALD1 and STX1A may be possible targets beneficial for the treatment of metastatic OS. However, further experimental studies are needed to confirm our results.