Molecular genetics of osteosarcoma

Rickel, Kirby; Fang, Fang; Tao, Jianning

doi:10.1016/j.bone.2016.10.017

Cited by 204 publications

(201 citation statements)

References 115 publications

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“…1 These incredibly complex hyperdiploid tumors are hallmarked by substantial genomic instability and highly prevalent chromothripsis. [2][3][4][5][6][7][8][9] However, despite our current understanding of the genomic characteristics of OS, the molecular and cellular mechanisms utilized by these tumors to modulate their microenvironment and favor disease progression is unknown.…”

Section: Introductionmentioning

confidence: 99%

Targeted transcriptional profiling of the tumor microenvironment reveals lymphocyte exclusion and vascular dysfunction in metastatic osteosarcoma

Sorenson

Hood

et al. 2019

OncoImmunology

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Osteosarcoma (OS) is the most common bone tumor in pediatric and adolescent/young adult patients yet little is known about the microenvironment that supports this aggressive disease. We have used targeted gene expression profiling and immunohistochemistry to characterize the microenvironment of metastatic and non-metastatic OS specimens from pediatric patients exhibiting poor histologic response to chemotherapy. Our results indicate that metastatic specimens exhibit lymphocyte exclusion as T cells are confined to the periphery of the pulmonary lesions. Furthermore, our data provides evidence of vascular dysfunction in metastatic OS indicated by increased expression of VEGFA, an increased ANGPT2: ANGPT1 gene expression ratio, and decreased expression of SELE, the gene encoding the adhesion molecule E-selectin. Moreover, correlation analyses show an inverse relationship between lymphocyte abundance and markers of vascular dysfunction exclusively in the metastatic specimens. Together, our data shows that the non-metastatic OS specimens demonstrate increased expression of various immunotherapeutic targets in comparison metastatic specimens and identifies vascular dysfunction and lymphocyte exclusion as important processes for therapeutic intervention in metastatic disease. ARTICLE HISTORY Results:Gene expression profiling of the tumor microenvironment and immuno-oncology landscape in pediatric OS Targeted gene expression profiling was performed on archived FFPE specimens from unmatched pediatric OS CONTACT Troy A. McEachron

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Section: Introductionmentioning

confidence: 99%

Targeted transcriptional profiling of the tumor microenvironment reveals lymphocyte exclusion and vascular dysfunction in metastatic osteosarcoma

Sorenson

Hood

et al. 2019

OncoImmunology

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“…A few years ago, all patients with osteosarcoma were treated with surgery, but the cure rate was <10% (17). Almost all patients died within one year after diagnosis and the disability rate and mortality were high (18). With the gradual development of molecular biology, miRNA has become a molecular biology indicator for the treatment strategy and prognosis of osteosarcoma (19).…”

Section: Discussionmentioning

confidence: 99%

Influence mechanism of miRNA‑144 on proliferation and apoptosis of osteosarcoma cells

Chen

Gao

et al. 2019

Oncol Lett

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Influence mechanism of miRNA-144 on proliferation and apoptosis of osteosarcoma cells was investigated. A total of 51 cases of osteosarcoma tissue samples were collected in the department of orthopedic surgery, Xuzhou Children's Hospital, Xuzhou Medical University from January 2014 to February 2017. Additionally, 48 cases of normal bone tissues were collected. qRT-PCR was used to detect the expression of miR-144. Correlation of miR-144 expression in serum and cancer tissues was detected. ROC curve was drawn to analyze the diagnostic value of miR-144 in patients with osteosarcoma. CCK-8 was used to detect the effect of miR-144 on the proliferation ability of U2-OS after transfection. The ratio of U2-OS apoptosis after miR-144 transfection was detected by flow cytometry. Western blot analysis was used to detect the expression of Bax, caspase-3 and Bcl-2 proteins in U2-OS after transfection. The relative expression of miR-144 in osteosarcoma and osteosarcoma serum was significantly lower than that in normal bone tissue and normal human serum (P<0.05). Serum in patients was positively correlated with the expression of miR-144 in cancer tissues. The area under the miR-144 curve was 0.852, 95% CI, 0.768-0.936. The relative expression of miR-144 in MG-63 and U2-OS cells was significantly lower than that in hFOB1.19 cells (P<0.05), while significantly lower in U2-OS cells than in MG-63 cells (P<0.05). Proliferation ability of U2-OS cells transfected with miR-144-mimics was significantly inhibited and the apoptosis rate was significantly increased (P<0.05). Bcl-2 protein was significantly decreased by detection of WB and the expression of Bax and caspase-3 protein was significantly increased (P<0.05). miR-144 may be involved in the occurrence and deterioration of osteosarcoma. miR-144 can regulate proliferation and apoptosis of U2-OS cells. It is expected to become a new diagnostic and index target for osteosarcoma.

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“…Authors' information 1 The Second Clinical Medical College, Lanzhou University, Lanzhou, Gansu 730000, PR China;…”

Section: Availability Of Data and Materialsmentioning

confidence: 99%

Identification of a novel autophagy-related gene signature for predicting metastasis and survival in patients with osteosarcoma

Zhang

Deng

et al. 2020

Preprint

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Background: Osteosarcoma (OS) is a bone malignant tumor that occurs in children and adolescents. Due to a lack of reliable prognostic biomarkers, the prognosis of OS patients is often uncertain. This study aimed to construct an autophagy-related gene signature to predict the prognosis of OS patients.Methods: The gene expression profile data of OS and normal muscle tissue samples were downloaded separately from the Therapeutically Applied Research To Generate Effective Treatments (TARGET) and Genotype-Tissue Expression (GTEx) databases . The differentially expressed autophagy-related genes (DEARGs) in OS and normal muscle tissue samples were screened using R software, before being subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. A protein-protein interaction (PPI) network was constructed and hub autophagy-related genes were screened. Finally, the screened autophagy-related genes were subjected to univariate Cox regression, Lasso Cox regression, survival analysis, and clinical correlation analysis.Results: A total of 120 DEARGs and 10 hub autophagy-related genes were obtained. A prognostic autophagy-related gene signature consisting of 9 genes ( BNIP3 , MYC , BAG1 , CALCOCO2 , ATF4 , AMBRA1 , EGFR , MAPK1 , and PEX ) was constructed. This signature was significantly correlated to the prognosis ( P <0.0001) and distant metastasis of OS patients ( P = 0.013).Conclusion: This signature based on 9 autophagy-related genes could predict metastasis and survival in patients with OS.

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Molecular genetics of osteosarcoma

Cited by 204 publications

References 115 publications

Targeted transcriptional profiling of the tumor microenvironment reveals lymphocyte exclusion and vascular dysfunction in metastatic osteosarcoma

Targeted transcriptional profiling of the tumor microenvironment reveals lymphocyte exclusion and vascular dysfunction in metastatic osteosarcoma

Influence mechanism of miRNA‑144 on proliferation and apoptosis of osteosarcoma cells

Identification of a novel autophagy-related gene signature for predicting metastasis and survival in patients with osteosarcoma

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