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1.
Cancer Med ; 10(13): 4493-4509, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34047495

RESUMO

BACKGROUND: Osteosarcoma is a tumour of malignant origin in children and adolescents. Recent progression indicates that it is necessary to develop new therapies to improve the patient's prognosis rather than strengthen anti-tumour chemotherapy. Researchers recently realised that cancer is a kind of disease with a metabolic disorder, and metabolic reprogramming is becoming a new cancer hallmark. Hence, our study's primary purpose is to explore the value of genes related to osteosarcoma metabolism. METHODS: From public databases, three osteosarcoma datasets with adequate clinical information were obtained. Besides, the IMvigor dataset through the 'IMvigor' package as a supplement was downloaded, the metabolic-related genes were identified, and these genes were used to construct the metabolic-related gene pairs (MRGP). Based on the prognosis-related MRGP, two molecular subtypes were identified. There are significant differences in the metabolic characteristics between the two molecular subtypes. Subsequently, the MRGP signature is constructed using the least absolute shrinkage and selection operator regression method. Finally, use SubMap analysis to evaluate the response of patients in the MRPG signature group to immunotherapy. RESULTS: The MRGP signature can reliably predict overall survival in patients with osteosarcoma. The MRGP signature is also associated with osteosarcoma patients' metastatic status and can be used for subsequent risk classification of metastatic patients. The immunotherapy is more likely to benefit the patients in the MRGP low-risk group. CONCLUSION: Metabolic-related gene pairs signature can assess the prognosis of patients with osteosarcoma.


Assuntos
Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Perfilação da Expressão Gênica , Osteossarcoma/genética , Osteossarcoma/metabolismo , Transcriptoma , Adolescente , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/terapia , Criança , Bases de Dados Genéticas , Feminino , Variação Genética , Humanos , Imunoterapia , Masculino , Nomogramas , Osteossarcoma/mortalidade , Osteossarcoma/terapia , Prognóstico , Análise de Regressão
2.
Aging (Albany NY) ; 12(22): 22906-22926, 2020 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-33203792

RESUMO

The purpose of this study is to establish the prognosis of osteosarcoma patients based on the characteristics of immune-related gene pairs. We used the lasso Cox regression model to construct and verify the signature consisting of 14 immune-related gene pairs. This signature can accurately predict the overall survival of osteosarcoma patients and is an independent prognostic factor for osteosarcoma patients. For this we constructed a signature-based nomogram. The results of the nomogram show that our signature can bring clinical net benefits. We then assessed the abundance of infiltrating immune cells in each sample, and combine the results of the gene set enrichment analysis of a single sample to explore the differences in the immune microenvironment between IRPG signature groups. The result of gene set enrichment analysis shows the strong relationship between signature and immune system. Finally, we evaluated the relationship between signature and immunotherapy efficiency using algorithms such as TIMI and SubMap to explore patients who might benefit from immunotherapy. In conclusion, our signature can predict the overall survival rate of osteosarcoma patients and provide potential guidance for exploring patients who may benefit from immunotherapy.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Ósseas/genética , Perfilação da Expressão Gênica , Nomogramas , Osteossarcoma/genética , Transcriptoma , Adolescente , Adulto , Antineoplásicos Imunológicos/uso terapêutico , Neoplasias Ósseas/imunologia , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/terapia , Tomada de Decisão Clínica , Bases de Dados Genéticas , Feminino , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia , Masculino , Osteossarcoma/imunologia , Osteossarcoma/mortalidade , Osteossarcoma/terapia , Valor Preditivo dos Testes , RNA-Seq , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Microambiente Tumoral , Adulto Jovem
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