AI Article Synopsis
- * The analysis revealed a trend where chemotherapy responders had a higher burden of chromosomal copy number variants (CNVs) and a greater percentage of a specific signature linked to DNA repair, compared to non-responders.
- * Transcriptomic data identified differing gene expression patterns between responders (11 up-regulated genes) and non-responders (18 up-regulated genes), indicating potential pathways influencing chemotherapy response and a promising avenue for future predictive research.
Article Abstract
Osteosarcoma is a heterogeneous disease with regard to its chemotherapy response and clinical outcomes. This study aims to investigate the genomic and transcriptomic characteristics related to pre-operative chemotherapy response. Samples from 25 osteosarcoma patients were collected to perform both whole exome and transcriptome sequencing. Osteosarcoma had significant amount of chromosomal copy number variants (CNVs). Chemotherapy responders showed the higher chromosomal CNV burden than non-responders (p = 0.0775), but the difference was not significant. The percentage of COSMIC signature 3, associated with homologous recombination repair deficiency, was higher in responders (56%) than in non-responders (45%). Transcriptomic analysis suggested that 11 genes were significantly up-regulated in responders and 18 genes were up-regulated in non-responders. Both GSEA and KEGG enrichment analysis indicted that four pathways related to cardiomyopathy were up-regulated in responders, while neuroactive ligand - receptor interaction was up-regulated in non-responders. Finally, a previously published chemoresistant model was validated using our dataset, with the area under the curve of 0.796 (95% CI, 0.583-1.000). Osteosarcoma had the heterogeneous mutational profile with frequent occurrence of CNVs. Transcriptomic analysis identified several signaling pathways associated with chemotherapy responsiveness to osteosarcoma. Transcriptomic signatures provides a potential research direction for predicting the chemotherapy response.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10684554 | PMC |
| http://dx.doi.org/10.1038/s41598-023-46857-8 | DOI Listing |
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