Origin and Therapies of Osteosarcoma

Moukengué, Brice; Lallier, Morgane; Marchandet, Louise; Baud’huin, Marc; Verrecchia, Franck; Ory, Benjamin; Lamoureux, François

doi:10.3390/cancers14143503

Cited by 38 publications

(35 citation statements)

References 283 publications

(311 reference statements)

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“…The complexity and diversity of OS itself not only bring difficulties to its diagnosis but also bring insurmountable obstacles to its treatment. At the same time, it also brings drug resistance during OS treatment and relapse after treatment [ 141 ]. Targeting specific driver genes is also problematic due to the high heterogeneity and low incidence of OS.…”

Section: Obstacles To Os Progress and Treatmentmentioning

confidence: 99%

Current Status and Prospects of Targeted Therapy for Osteosarcoma

Wen

Huo

et al. 2022

Cells

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Osteosarcoma (OS) is a highly malignant tumor occurring in bone tissue with a high propensity to metastasize, and its underlying mechanisms remain largely elusive. The OS prognosis is poor, and improving the survival of OS patients remains a challenge. Current treatment methods such as surgical approaches, chemotherapeutic drugs, and immunotherapeutic drugs remain ineffective. As research progresses, targeted therapy is gradually becoming irreplaceable. In this review, several treatment modalities for osteosarcoma, such as surgery, chemotherapy, and immunotherapy, are briefly described, followed by a discussion of targeted therapy, the important targets, and new technologies for osteosarcoma treatment.

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Section: Obstacles To Os Progress and Treatmentmentioning

confidence: 99%

Current Status and Prospects of Targeted Therapy for Osteosarcoma

Wen

Huo

et al. 2022

Cells

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“…Additionally, more than 30% of these patients show metastases at initial diagnosis. Although OS with an integrated treatment plan shows a 5-year survival rate of 70%, once the patient develops metastasis or the treatment fails, the overall survival rate drops significantly to 20-30% ( 2 ). Tracing back to the source, the primary cause of treatment failure and mortality in patients with OS is the high metastatic potential in combination with the high tumoral heterogeneity.…”

Section: Introductionmentioning

confidence: 99%

The hexosamine biosynthesis pathway-related gene signature correlates with immune infiltration and predicts prognosis of patients with osteosarcoma

Wang

Pan

et al. 2022

Front. Immunol.

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ObjectivesOsteosarcoma is a malignant bone tumor with poor outcomes affecting the adolescents and elderly. In this study, we comprehensively assessed the metabolic characteristics of osteosarcoma patients and constructed a hexosamine biosynthesis pathway (HBP)-based risk score model to predict the prognosis and tumor immune infiltration in patients with osteosarcoma.MethodsGene expression matrices of osteosarcoma were downloaded from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Gene Expression Omnibus (GEO) databases. GSVA and univariate Cox regression analysis were performed to screen the metabolic features associated with prognoses. LASSO regression analysis was conducted to construct the metabolism-related risk model. Differentially expressed genes (DEGs) were identified and enrichment analysis was performed based on the risk model. CIBERSORT and ESTIMATE algorithms were executed to evaluate the characteristics of tumor immune infiltration. Comparative analyses for immune checkpoints were performed and the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm was used to predict immunotherapeutic response. Finally, hub genes with good prognostic value were comprehensive analyzed including drug sensitivity screening and immunohistochemistry (IHC) experiments.ResultsThrough GSVA and survival analysis, the HBP pathway was identified as the significant prognostic related metabolism feature. Five genes in the HBP pathway including GPI, PGM3, UAP1, OGT and MGEA5 were used to construct the HBP-related risk model. Subsequent DEGs and enrichment analyses showed a strong correlation with immunity. Further, CIBERSORT and ESTIMATE algorithms showed differential immune infiltration characteristics correlated with the HBP-related risk model. TIDE algorithms and immune checkpoint analyses suggested poor immunotherapeutic responses with low expression of immune checkpoints in the high-risk group. Further analysis revealed that the UAP1 gene can predict metastasis. IHC experiments suggested that UAP1 expression correlated significantly with the prognosis and metastasis of osteosarcoma patients. When screening for drug sensitivity, high UAP1 expression was suggestive of great sensitivity to antineoplastic drugs including cobimetinib and selumetinib.ConclusionWe constructed an HBP-related gene signature containing five key genes (GPI, PGM3, UAP1, OGT, MGEA5) which showed a remarkable prognostic value for predicting prognosis and can guide immunotherapy and targeted therapy for osteosarcoma.

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“…Osteosarcoma is an advanced malignant stromal tumor composed of mesenchymal cells that produce osteoid and immature bone, accounting for 3–6% of childhood cancers and 1% of adult cancers ( 1 , 2 ). The combination of surgery and chemotherapy greatly has improved the prognosis of patients with osteosarcoma, and the overall survival (OS) has reached 70%.…”

Section: Introductionmentioning

confidence: 99%

“…No effective treatment has been developed to improve the treatment of osteosarcoma for more than 30 years ( 6 ). At present, the difficulty of designing and verifying new therapies in osteosarcoma lies in 2 levels of complexity, the most important of which is that the pathology is highly heterogeneous and there are no obvious targeted events ( 2 , 7 ). However, most immunotherapies have not reached the desired level of success in the treatment of osteosarcoma.…”

Section: Introductionmentioning

confidence: 99%

Characterization of osteosarcoma subtypes mediated by macrophage-related genes and creation and validation of a risk score system to quantitatively assess the prognosis of osteosarcoma and reflect the tumor microenvironment

Liu¹,

Zhang²,

Zhong³

2022

Ann Transl Med

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Background: Macrophages are the main immune components in the microenvironment of osteosarcoma.The treatment strategy centered on macrophages has become a hot topic to improve cancer treatment.However, the research on the role of macrophages in the treatment of osteosarcoma is still in its infancy. Methods:The data of osteosarcoma samples were downloaded from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and GSE21257 datasets, and the macrophage enrichment fraction of osteosarcoma samples in TARGET was calculated by single-sample gene set enrichment analysis (ssGSEA) method to screen macrophage-related genes for consensus clustering.Differential expression analysis, univariable Cox, and least absolute shrinkage and selection operator (LASSO) regression were conducted to select reliable predictors and create a risk score system. The GSE21257 dataset was used as a verification set to verify the accuracy of risk score system. Results:We identified 2 osteosarcoma clusters mediated by 22 macrophage score-related genes, namely cluster 1 (C1) and cluster 2 (C2). Compared with C2, C1 had a significant advantage in prognosis, and the degree of immune cell infiltration in tumor microenvironment (TME) was significantly higher, the expression of immune checkpoint molecules was significantly enhanced, and the Tumor Immune Dysfunction and Exclusion (TIDE) score was also significantly down-regulated. A robust risk score system was presented and validated, which demonstrated accuracy and independence in assessing the risk of death of osteosarcoma. The risk score system could also monitor TME infiltration in osteosarcoma samples and showed a close relationship with osteosarcoma biology, including metastasis and immunity. Conclusions:We identified 2 types of clusters mediated by macrophage-related genes and helped to analyze the cluster suitable for immunotherapy. A new prognostic risk score system was created to quantitatively evaluate the prognosis and TME of osteosarcoma, and to provide a new entry point for the design of personalized treatment.

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Origin and Therapies of Osteosarcoma

Cited by 38 publications

References 283 publications

Current Status and Prospects of Targeted Therapy for Osteosarcoma

Current Status and Prospects of Targeted Therapy for Osteosarcoma

The hexosamine biosynthesis pathway-related gene signature correlates with immune infiltration and predicts prognosis of patients with osteosarcoma

Characterization of osteosarcoma subtypes mediated by macrophage-related genes and creation and validation of a risk score system to quantitatively assess the prognosis of osteosarcoma and reflect the tumor microenvironment

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