Identification of Osteosarcoma Metastasis-Associated Gene Biomarkers and Potentially Targeted Drugs Based on Bioinformatic and Experimental Analysis
| Autor: | Da-Wei Wang, Hua-Ding Lu, Yi-Ming Lin, Yan-Cheng Song, Zhong-Meng Yang, Ming-De Cao |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
migration OncoTargets and Therapy metastatic-related signatures Interleukin 10 receptor alpha subunit Metastasis 03 medical and health sciences 0302 clinical medicine drug–gene interaction osteosarcoma medicine Pharmacology (medical) Gene Original Research TLR7 Cause of death Proportional hazards model business.industry virus diseases invasion medicine.disease 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer research Osteosarcoma Identification (biology) business |
| Zdroj: | OncoTargets and therapy |
| ISSN: | 1178-6930 |
| Popis: | Ming-De Cao,1 Yan-Cheng Song,2 Zhong-Meng Yang,1 Da-Wei Wang,1 Yi-Ming Lin,1 Hua-Ding Lu1 1Department of Orthopaedics, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai 519000, Guangdong, People’s Republic of China; 2Department of Orthopedics, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510000, Guangdong, People’s Republic of ChinaCorrespondence: Hua-Ding LuDepartment of Orthopaedics, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai 519000, Guangdong, People’s Republic of ChinaTel +86 13807918420Email johnniehuading@163.comBackground: Metastasis is the leading cause of death for patients with osteosarcoma (OS). In the present study, we explore the biomarkers for metastatic OS and provide potential therapeutic approaches.Materials and Methods: RNA-Seq data and clinical follow-up information were downloaded from TARGET and GEO databases. A Cox regression model was used to analyze metastatic events. L1000FWD, DGIdb, and CMap databases were used to identify potential drugs related to metastasis. Invasion and migration transwell assays and an adhesion assay were used to identify biological functions of genes.Results: A total of 15 metastasis-related signatures (MRSs) were associated with the prognosis based on the TARGET or GSE21257 cohorts, among which IL10RA and TLR7 genes were especially significant. In the DGIdb drug–gene interaction database, TLR7 and IFNGR1 were found to have potential interactions with drugs. After inhibiting the expression of TLR7, the migration, invasion, and adhesion ability of OS cells were significantly enhanced, which further promoted metastasis.Conclusion: We identified a set of MRS that may be related to OS metastases. Among them, TLR7 plays a vital role and may be a potential target for OS metastasis treatment.Keywords: osteosarcoma, metastatic-related signatures, drug–gene interaction, TLR7, migration, invasion |
| Databáze: | OpenAIRE |
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