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基于生物信息学方法鉴定与骨肉瘤转移和预后相关的枢纽基因并构建预后模型。

Identification of hub genes related to metastasis and prognosis of osteosarcoma and establishment of a prognostic model with bioinformatic methods.

机构信息

Department of Orthopedics, Binzhou People's Hospital, Binzhou,China.

Department of Orthopedics, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

出版信息

Medicine (Baltimore). 2024 Jun 7;103(23):e38470. doi: 10.1097/MD.0000000000038470.

Abstract

Osteosarcoma (OS) is the most common primary malignant bone tumor occurring in children and adolescents. Improvements in our understanding of the OS pathogenesis and metastatic mechanism on the molecular level might lead to notable advances in the treatment and prognosis of OS. Biomarkers related to OS metastasis and prognosis were analyzed and identified, and a prognostic model was established through the integration of bioinformatics tools and datasets in multiple databases. 2 OS datasets were downloaded from the Gene Expression Omnibus database for data consolidation, standardization, batch effect correction, and identification of differentially expressed genes (DEGs); following that, gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the DEGs; the STRING database was subsequently used for protein-protein interaction (PPI) network construction and identification of hub genes; hub gene expression was validated, and survival analysis was conducted through the employment of the TARGET database; finally, a prognostic model was established and evaluated subsequent to the screening of survival-related genes. A total of 701 DEGs were identified; by gene ontology and KEGG pathway enrichment analyses, the overlapping DEGs were enriched for 249 biological process terms, 13 cellular component terms, 35 molecular function terms, and 4 KEGG pathways; 13 hub genes were selected from the PPI network; 6 survival-related genes were identified by the survival analysis; the prognostic model suggested that 4 genes were strongly associated with the prognosis of OS. DEGs related to OS metastasis and survival were identified through bioinformatics analysis, and hub genes were further selected to establish an ideal prognostic model for OS patients. On this basis, 4 protective genes including TPM1, TPM2, TPM3, and TPM4 were yielded by the prognostic model.

摘要

骨肉瘤(OS)是儿童和青少年中最常见的原发性恶性骨肿瘤。在分子水平上对 OS 发病机制和转移机制的深入了解可能会显著改善 OS 的治疗和预后。分析和鉴定了与 OS 转移和预后相关的生物标志物,并通过整合多个数据库中的生物信息学工具和数据集建立了预后模型。从基因表达综合数据库中下载了 2 个 OS 数据集,用于数据整合、标准化、批次效应校正和差异表达基因(DEGs)的鉴定;随后对 DEGs 进行基因本体论和京都基因与基因组百科全书(KEGG)通路富集分析;随后使用 STRING 数据库构建蛋白质-蛋白质相互作用(PPI)网络并鉴定枢纽基因;通过 TARGET 数据库验证枢纽基因表达并进行生存分析;最后,筛选生存相关基因后建立并评估预后模型。共鉴定出 701 个 DEGs;通过基因本体论和 KEGG 通路富集分析,重叠的 DEGs 富集了 249 个生物学过程术语、13 个细胞成分术语、35 个分子功能术语和 4 个 KEGG 通路;从 PPI 网络中选择了 13 个枢纽基因;通过生存分析鉴定了 6 个与生存相关的基因;预后模型表明,4 个基因与 OS 预后密切相关。通过生物信息学分析鉴定了与 OS 转移和生存相关的 DEGs,并进一步选择枢纽基因建立 OS 患者理想的预后模型。在此基础上,该预后模型产生了包括 TPM1、TPM2、TPM3 和 TPM4 在内的 4 个保护性基因。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6eb/11155596/cebe3c65f45b/medi-103-e38470-g001.jpg

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