BackgroundSpinal chordomas are rare primary osseous tumors that arise from the remnants of the notochord. They are commonly considered slow-growing, locally invasive neoplasms with little tendency to metastasize, but the high recurrent rate of spinal chordomas may seriously affect the survival rate and quality of life of patients. The aim of the study is to describe the epidemiological data and determine the prognostic factors for decreased survival in patients with primary spinal chordoma.MethodsThe Surveillance, Epidemiology, and End Results (SEER) Registry database, a US population-based cancer registry database, was used to identify all patients diagnosed with primary spinal chordoma from 1973 to 2014. We utilized Kaplan–Meier method and Cox proportional hazards regression analysis to evaluate the association between patients overall survival and relevant characteristics, including age, gender, race, disease stage, treatment methods, primary tumor site, marital status, and urban county background.ResultsIn the data set between 1973 and 2014, a total of 808 patients were identified with primary spinal chordoma. The overall rate of distant metastatic cases in our cohort was only 7.7%. Spinal chordoma was more common occurred in men (62.6%) than women (37.3%). Majority of neoplasms were found in the White (87.9%), while the incidence of the Black is relatively infrequent (3.3%). Three hundred fifty-seven spinal chordomas (44.2%) were located in the vertebral column, while 451 patients’ tumor (55.8%) was located in the sacrum or pelvis. Age ≥ 60 years (HR = 2.72; 95%CI, 1.71 to 2.89), distant metastasis (HR = 2.16; 95%CI, 1.54 to 3.02), and non-surgical therapy (HR = 2.14; 95%CI, 1.72 to 2.69) were independent risk factors for survival reduction in analysis. Survival did not significantly differ as a factor of tumor site (vertebrae vs sacrum/pelvis) for primary spinal chordoma (HR = 0.93, P = 0.16). Race (P = 0.52), gender (P = 0.11), marital status (P = 0.94), and urban background (P = 0.72) were not main factors which affected overall survival rate.ConclusionThere was no significant difference in overall survival rate between chordomas located in the sacrum and vertebral column. Spinal chordoma patients with an elderly age (age ≥ 60), performing non-surgical therapy, and distant metastasis were associated with worse overall survival. Performing surgery was an effective and reliable treatment method for patients with spinal chordoma, and public health efforts should pay more attention to the elderly patients with spinal chordoma prior to distant metastasis.

BackgroundThis study aimed to identify potential crucial genes and construction of microRNA-mRNA negative regulatory networks in osteosarcoma by comprehensive bioinformatics analysis.MethodsData of gene expression profiles (GSE28424) and miRNA expression profiles (GSE28423) were downloaded from GEO database. The differentially expressed genes (DEGs) and miRNAs (DEMIs) were obtained by R Bioconductor packages. Functional and enrichment analyses of selected genes were performed using DAVID database. Protein–protein interaction (PPI) network was constructed by STRING and visualized in Cytoscape. The relationships among the DEGs and module in PPI network were analyzed by plug-in NetworkAnalyzer and MCODE seperately. Through the TargetScan and comparing target genes with DEGs, the miRNA-mRNA regulation network was established.ResultsTotally 346 DEGs and 90 DEMIs were found to be differentially expressed. These DEGs were enriched in biological processes and KEGG pathway of inflammatory immune response. 25 genes in the PPI network were selected as hub genes. Top 10 hub genes were TYROBP, HLA-DRA, VWF, PPBP, SERPING1, HLA-DPA1, SERPINA1, KIF20A, FERMT3, HLA-E. PPI network of DEGs followed a pattern of power law network and met the characteristics of small-world network. MCODE analysis identified 4 clusters and the most significant cluster consisted of 11 nodes and 55 edges. SEPP1, CKS2, TCAP, BPI were identified as the seed genes in their own clusters, respectively. The miRNA-mRNA regulation network which was composed of 89 pairs was established. MiR-210 had the highest connectivity with 12 target genes. Among the predicted target of MiR-96, HLA-DPA1 and TYROBP were the hub genes.ConclusionOur study indicated possible differentially expressed genes and miRNA, and microRNA-mRNA negative regulatory networks in osteosarcoma by bioinformatics analysis, which may provide novel insights for unraveling pathogenesis of osteosarcoma.

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Many neurodegenerative diseases are related to copper although the effects on brain microvascular endothelial cells (BMECs) are poorly understood. In the present study, a primary BMEC culture model was established to evaluate the effects of copper on brain microvascular endothelial cells and whether claudin-1, claudin-3, claudin-5, and claudin-12 isoforms contribute to apoptosis and intrinsic antioxidant activity. Our results showed that copper ions had dual effects on BMECs by regulating intracellular reactive oxygen species (ROS) levels. Copper levels between 30 and 120 μM could enhance viability and promote proliferation. On the other hand, copper cytotoxicity was a result of apoptosis indicating a redox-independent manner of cell death. Expression levels of claudins were also regulated by copper in a concentration-dependent manner. We identified four claudin isoforms (1, 3, 5, and 12) and showed that their expression levels were regulated as a group by copper. Antioxidant activity of BMECs was also copper regulated, and superoxide dismutase and catalase were the main contributors to BMEC antioxidant functions. Together, our results indicated that copper had dual effects on BMEC growth and intrinsic antioxidant activities played a crucial role in BMEC survival and tight junction.

Sorafenib is an inhibitor of a variety of tyrosine kinase receptors used to treat various cancers including hepatocellular, renal cell and thyroid carcinoma. It has been shown to change various targets associated with osteosarcoma, but the detailed mechanism remains unclear. In order to identify key genes, enriched pathways and important modules during the exposure of human osteosarcoma cells to sorafenib, data for gene expression profiles ( http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE53155 ) were downloaded from the GEO database. In total, 61 differentially expressed genes ( DEG s) were identified by the R bioconductor packages. Functional and enrichment analyses of DEG s were performed using the DAVID database. These revealed that DEG s were enriched in biological processes, molecular function and KEGG pathway of inflammatory immune response and angiogenesis. A protein–protein interaction network was constructed by string and visualized in cytoscape , and eight genes were selected as hubs: IL 8 , CXCL 2 , PTGS 2 , FOS , CXCL 1 , C3 , EHMT 2 and PGF . Subsequently, only one cluster was identified by mcode , which consisted of six nodes ( CXCL 1 , CXCL 2 , PTGS 2 , FOS , C3 and PGF ) and nine edges. PGF was the seed gene in this cluster. In conclusion, the results of this data mining and integration should help in revealing new mechanisms and targets of sorafenib in inhibiting osteosarcoma.

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