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      Identification of potential crucial genes and key pathways in osteosarcoma

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          Abstract

          Background

          The aim of this study is to identify the potential pathogenic and metastasis-related differentially expressed genes (DEGs) in osteosarcoma through bioinformatic analysis of Gene Expression Omnibus (GEO) database.

          Results

          Gene expression profiles of GSE14359, GSE16088, and GSE33383, in total 112 osteosarcoma tissue samples and 7 osteoblasts, were analyzed. Seventy-four normal-primary DEGs (NPDEGs) and 764 primary-metastatic DEGs (PMDEGs) were screened. VAMP8, A2M, HLA-DRA, SPARCL1, HLA-DQA1, APOC1 and AQP1 were identified continuously upregulating during the oncogenesis and metastasis of osteosarcoma. The enriched functions and pathways of NPDEGs include procession and presentation of antigens, activation of MHC class II receptors and phagocytosis. The enriched functions and pathways of PMDEGs include mitotic nuclear division, cell adhesion molecules (CAMs) and focal adhesion. With protein-protein interaction (PPI) network analyzed by Molecular Complex Detection (MCODE) plug-in of Cytoscape software, one hub NPDEG (HLA-DRA) and 7 hub PMDEGs (CDK1, CDK20, CCNB1, MTIF2, MRPS7, VEGFA and EGF) were eventually selected, and the most significant pathways in NPDEGs module and PMDEGs module were enriched in the procession and presentation of exogenous peptide antigen via MHC class II and the nuclear division, respectively.

          Conclusions

          By integrated bioinformatic analysis, numerous DEGs related to osteosarcoma were screened, and the hub DEGs identified in this study are possibly part of the potential biomarkers for osteosarcoma. However, further experimental studies are still necessary to elucidate the biological function and mechanism of these genes.

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          Most cited references44

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          Canine tumor cross-species genomics uncovers targets linked to osteosarcoma progression

          Background Pulmonary metastasis continues to be the most common cause of death in osteosarcoma. Indeed, the 5-year survival for newly diagnosed osteosarcoma patients has not significantly changed in over 20 years. Further understanding of the mechanisms of metastasis and resistance for this aggressive pediatric cancer is necessary. Pet dogs naturally develop osteosarcoma providing a novel opportunity to model metastasis development and progression. Given the accelerated biology of canine osteosarcoma, we hypothesized that a direct comparison of canine and pediatric osteosarcoma expression profiles may help identify novel metastasis-associated tumor targets that have been missed through the study of the human cancer alone. Results Using parallel oligonucleotide array platforms, shared orthologues between species were identified and normalized. The osteosarcoma expression signatures could not distinguish the canine and human diseases by hierarchical clustering. Cross-species target mining identified two genes, interleukin-8 (IL-8) and solute carrier family 1 (glial high affinity glutamate transporter), member 3 (SLC1A3), which were uniformly expressed in dog but not in all pediatric osteosarcoma patient samples. Expression of these genes in an independent population of pediatric osteosarcoma patients was associated with poor outcome (p = 0.020 and p = 0.026, respectively). Validation of IL-8 and SLC1A3 protein expression in pediatric osteosarcoma tissues further supported the potential value of these novel targets. Ongoing evaluation will validate the biological significance of these targets and their associated pathways. Conclusions Collectively, these data support the strong similarities between human and canine osteosarcoma and underline the opportunities provided by a comparative oncology approach as a means to improve our understanding of cancer biology and therapies.
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            The Immunology of CD1- and MR1-Restricted T Cells.

            CD1- and MHC-related molecule-1 (MR1)-restricted T lymphocytes recognize nonpeptidic antigens, such as lipids and small metabolites, and account for a major fraction of circulating and tissue-resident T cells. They represent a readily activated, long-lasting population of effector cells and contribute to the early phases of immune response, orchestrating the function of other cells. This review addresses the main aspects of their immunological functions, including antigen and T cell receptor repertoires, mechanisms of nonpeptidic antigen presentation, and the current evidence for their participation in human and experimental diseases.
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              Tumor cell-targeted delivery of CRISPR/Cas9 by aptamer-functionalized lipopolymer for therapeutic genome editing of VEGFA in osteosarcoma

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                Author and article information

                Contributors
                dr_wangziming@163.com
                qianqianlei0420@yahoo.com
                Journal
                Hereditas
                Hereditas
                Hereditas
                BioMed Central (London )
                0018-0661
                1601-5223
                14 July 2020
                14 July 2020
                2020
                : 157
                : 29
                Affiliations
                [1 ]GRID grid.414048.d, ISNI 0000 0004 1799 2720, Department of Orthopedic surgery, , Daping Hospital, Army medical university, ; No. 10 Changjiang Branch Road, Yuzhong District, Chongqing, 400042 PR China
                [2 ]GRID grid.190737.b, ISNI 0000 0001 0154 0904, Department of Radiation Oncology, , Chongqing University Cancer Hospital, ; No. 181, Hanyu road, Shapingba District, Chongqing, 400030 PR China
                Author information
                http://orcid.org/0000-0002-2440-9412
                Article
                142
                10.1186/s41065-020-00142-0
                7362476
                32665038
                dc78b44a-e2ac-4b81-a565-6ea25d33ace3
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 17 March 2020
                : 3 July 2020
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100012669, Natural Science Foundation Project of Chongqing, Chongqing Science and Technology Commission;
                Award ID: cstc2019jcyj-msxmX0648
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2020

                osteosarcoma,gene expression omnibus,differentially expressed genes,bioinformatics,pathway

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