Analysis Of Somatic Variants And TMB-related Prognosis In Osteosarcoma By Whole-exome Sequencing

Background and ObjectiveOsteosarcoma is a rare tumor with extremely high degree of malignancy,with a low 5-year survival rate and a high rate of metastasis and recurrence.The traditional operation and neoadjuvant chemoradiotherapy cannot achieve satisfactory therapeutic effect.With the development of sequencing technology,we began to solve the problem from the perspective of molecular biology.The purpose of this study was to explore the role of gene mutation type,biological function,pathway enrichment and analysis in the occurrence and development of osteosarcoma,as well as the relationship between TMB and prognosis,so as to further guide clinical treatment.MethodsSomatic mutation screening was carried out by whole exome sequencing technology of osteosarcoma genomic DNA.GO analysis,KEGG signaling pathway enrichment analysis and PPI network mapping were performed for mutated genes with altered codes by Metascape.Search for common mutations and analyze their mutation types.The correlation between TMB and PFS was analyzed to evaluate the prognosis.ResultsThere were a large number of the same or related biological processes and pathways enrichment locally in 9 osteosarcoma samples,which played a key role in the development of gene expression tumors.Among them,the regulation of GTPas activity was enriched in 8 samples,which was related to the regulation of osteosarcoma cell signals to tumor survival and migration.The more enriched the biological processes and pathways associated with osteosarcoma,the worse the prognosis.After screening,the driver genes of osteosarcoma were somatic mutations.TP53,GNAS,EGFR,BRCA1,RECQL4 and RECQL5 were all mutated in the coding region of local samples,among which the mutation types of TP53,RECQL4 and RECQL5 were missense mutations.TP53 was mutated in 3 patients and RECQL4 and RECQL5 were mutated in 1 patient respectively.In the correlation analysis,TMB was basically negatively correlated with PFS(R=0.8555).The higher the TMB,the worse the prognosis in patients with osteosarcoma without immunotherapy.ConclusionThrough gene analysis,it was confirmed that there are common and extensive gene mutations in patients with osteosarcoma.These mutations were related to each other and participate in tumor-related metabolic pathways.The level of TMB may determine the prognosis and predict the efficacy,providing reference for the selection of gene targeting or immunotherapy in the future.