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- W4319736936 abstract "Abstract Background Osteosarcoma (OS) is the most frequent and aggressive primary malignant sarcoma among adolescents and chemotherapy has not substantially progressed for decades. New insights into OS development and therapeutic strategies are urgently needed. Methods We analyzed integrated single-cell transcriptomes, bulk RNA-seq, and microarray data from Gene Expression Omnibus (GEO) datasets. We also used Weighted Gene Co-expression Network Analysis (WGCNA), Gene set enrichment analysis (GSEA), and Gene set variation analysis (GSVA), along with Simple ClinVar and Enrichr web servers. Results The findings of integrated single-cell analysis showed that OS arises from imperfect osteogenesis during development. Novel abnormalities comprised deficient TGFβ and P53 signal pathways, and cell cycle pathway activation, and a potentially new driver mutation in the interferon induced transmembrane protein 5 ( IFITM5 ) that might function as a pathogenic factor in OS. Osteosarcoma is characterized by oncocyte heterogeneity, especially in immunogenic and adipocyte-like subtypes that respectively promote and hamper OS treatment. Etoposide is a promising chemotherapeutic that provides palliation by affecting the subtype of OS and correcting the abnormal pathways. Conclusion Various abnormal signal pathways play indispensable roles in OS development. We explored the heterogeneity and underlying mechanisms of OS and generated findings that will assist with OS assessment and selecting optimal therapies." @default.
- W4319736936 created "2023-02-11" @default.
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- W4319736936 date "2023-02-09" @default.
- W4319736936 modified "2023-09-30" @default.
- W4319736936 title "Abnormal signal pathways and tumor heterogeneity in osteosarcoma" @default.
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- W4319736936 doi "https://doi.org/10.1186/s12967-023-03961-7" @default.
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