Analysis of the Mutational Landscape of Osteosarcomas Identifies Genes Related to Metastasis and Prognosis and Disrupted Biological Pathways of Immune Response and Bone Development

Pires, Sara Ferreira; Barros, Juliana Sobral de; Costa, Silvia Souza da; Carmo, Gabriel Bandeira do; Scliar, Marília de Oliveira; Lengert, André van Helvoort; Boldrini, Érica; Silva, Sandra R.M. da; Vidal, Daniel Onofre; Maschietto, Mariana; Krepischi, Ana Cristina Victorino

doi:10.3390/ijms241310463

Cited by 3 publications

(2 citation statements)

References 87 publications

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“…Moreover, a recent study showed how the WES analysis in osteosarcoma is able to identify alteration in genes involved in the protein-protein networking on specific pathways implicated in skeletal system development [63].…”

Section: Discussionmentioning

confidence: 99%

Advances in Target Therapy Research in Osteosarcoma

Chiappetta,

Della Rocca,

Di Cristofano

2024

Preprint

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Osteosarcoma (OS) are the most prevalent malignant bone tumors in adolescents and young adults.. OS cells grow in a permissive local microenvironment which modulates their behavior and facilitates all steps in tumor development (e.g., proliferation/quiescence, invasion/migration, drug resistance) and contributes to their intrinsic heterogeneity. The lung parenchyma is the most common metastatic site in OS, and metastatic foci are frequently associated with a poor clinical outcome. Although multiple factors may be responsible for the disease, including genetic mutations (e.g., Rb, p53), the molecular mechanism of development of OS remains unclear and the conventional treatment for OS is still based on a sequential approach that combines chemotherapy and surgery. Also, despite the increase in clinical trials, the survival rates for OS have not improved. Non-specific targeting therapies thus show poor therapeutic effects with side effects at high doses. For these reasons, many efforts have been done to characterize the complex genome of osteosarcoma thanks to the whole exome analysis with the aim to identify predictive biomarkers to give to these patients a better therapeutic option. This review aims to summarize and discuss the main recent advances in OS molecular research for precision medicine.

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Section: Discussionmentioning

confidence: 99%

Advances in Target Therapy Research in Osteosarcoma

Chiappetta,

Della Rocca,

Di Cristofano

2024

Preprint

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“…Another group found that PD-L1 was induced by IRF8 and that in human OSA cells, PD-L1 and IRF8 were involved in growth and tumorigenicity, and that PD-L1 knockdown combined with doxorubicin treatment resulted in inhibition of cell growth [76]. Furthermore, a study identified that IRF8 was among one of the many genes deleted in >25% of cases, according to an analysis of 28 human OSA samples [77]. Our current study presents the expression of IFR8 in canine OSA.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical Investigation into Protein Expression Patterns of FOXO4, IRF8 and LEF1 in Canine Osteosarcoma

Brot,

Cobb,

Alibhai

et al. 2024

Cancers

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Osteosarcoma (OSA) is the most common type of primary bone malignancy in people and dogs. Our previous molecular comparisons of canine OSA against healthy bone resulted in the identification of differentially expressed protein-expressing genes (forkhead box protein O4 (FOXO4), interferon regulatory factor 8 (IRF8), and lymphoid enhancer binding factor 1 (LEF1)). Immunohistochemistry (IHC) and H-scoring provided semi-quantitative assessment of nuclear and cytoplasmic staining alongside qualitative data to contextualise staining (n = 26 patients). FOXO4 was expressed predominantly in the cytoplasm with significantly lower nuclear H-scores. IRF8 H-scores ranged from 0 to 3 throughout the cohort in the nucleus and cytoplasm. LEF1 was expressed in all patients with significantly lower cytoplasmic staining compared to nuclear. No sex or anatomical location differences were observed. While reduced levels of FOXO4 might indicate malignancy, the weak or absent protein expression limits its primary use as diagnostic tumour marker. IRF8 and LEF1 have more potential for prognostic and diagnostic uses and facilitate further understanding of their roles within their respective molecular pathways, including Wnt/beta-catenin/LEF1 signalling and differential regulation of tumour suppressor genes. Deeper understanding of the mechanisms involved in OSA are essential contributions towards the development of novel diagnostic, prognostic, and treatment options in human and veterinary medicine contexts.

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The importance of basic and translational research in caring for children with malignant solid tumors in Latin America

Cancela,

Dinardi,

Aschero

et al. 2024

Revista Panamericana De Salud Pública

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Objective. Basic and translational research in pediatric cancer are essential to improve patient care. To critically assess the developments achieved in these areas in Latin America, we systematically reviewed information published between 2013 and 2023. Methods. Studies of basic and translational research performed by investigators in Latin America evaluating pediatric malignant solid and central nervous system tumors were retrieved from PubMed. Original articles published in English between 2013 and 2023 were included. Collaborations among Latin American authors or among Latin American authors working with researchers from other continents were also included. Studies were excluded if they focused only on adults or on basic research in tumor biology not specifically related to the tumor types analyzed in this review. Results. A total of 550 articles were retrieved, but after removal of duplicates, 514 articles were included in the analysis, the majority of which were authored by researchers affiliated with institutions in Argentina, Brazil and Mexico. These countries also had the highest number of collaborations on original articles published with authors from Europe and North America. Argentina had the highest number of collaborations on original publications, with coauthors from Brazil and Uruguay. The median impact factor of the 244 journals in which articles were published was 3.5. The most commonly studied tumors were osteosarcomas, neuroblastomas and medulloblastomas; the most commonly studied areas were molecular analysis, tumor cell biology and biomarkers. Conclusions. In Latin America, research in pediatric oncology is on the agenda, despite a notable disparity in publication rates and frequency of collaboration between countries. There is a need to strengthen scientific collaboration within Latin America and with countries from other continents to promote research and to develop novel treatment strategies that reflect the local needs of children in Latin America who have solid tumors and brain cancer.

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Analysis of the Mutational Landscape of Osteosarcomas Identifies Genes Related to Metastasis and Prognosis and Disrupted Biological Pathways of Immune Response and Bone Development

Cited by 3 publications

References 87 publications

Advances in Target Therapy Research in Osteosarcoma

Advances in Target Therapy Research in Osteosarcoma

Immunohistochemical Investigation into Protein Expression Patterns of FOXO4, IRF8 and LEF1 in Canine Osteosarcoma

The importance of basic and translational research in caring for children with malignant solid tumors in Latin America

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