Integrative genomic analysis of matched primary and metastatic pediatric osteosarcoma

Grande, Bruno M.; Delaidelli, Alberto; El-Naggar, Amal M.; Cochrane, Dawn R.; Lau, Ching C.; Triche, Timothy J.; Moore, Richard A.; Jones, Steven J.M.; Montpetit, Alexandre; Marra, Marco A.; Malkin, David; Morin, Ryan D.; Sorensen, Poul H.

doi:10.1002/path.5319

Cited by 44 publications

(38 citation statements)

References 71 publications

(115 reference statements)

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“…Though the surgery, chemotherapy, and targeted drugs offer symptomatic relief and modest improvement in survival for OS patients, the overall survival rate remains unfavourable . It is widely believed that further research on the underlying mechanisms of OS and the search for novel therapeutic targets are highly desirable to improve the prognosis of OS patients . In this study, a novel circRNA, circ_0001658, was studied for the first time, and it was demonstrated to be upregulated in OS tissues and cells.…”

Section: Discussionmentioning

confidence: 93%

Circ_0001658 promotes the proliferation and metastasis of osteosarcoma cells via regulating miR‐382‐5p/YB‐1 axis

Wang

et al. 2019

Cell Biochemistry & Function

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Circular RNA (circRNA) can modulate the gene expression via sponging microRNA (miRNA) in multiple malignancies. Nevertheless, the detailed function of circ_0001658 in osteosarcoma (OS) and its regulatory mechanism remain elusive.Real-time PCR was carried out to detect the expressions of circ_0001658, miR-382-5p, and Y box-binding protein 1 (YB-1) mRNA in OS tissues. Besides, western blot was done to monitor YB-1 expression in OS cells. Chi-squared test was used to analyse the correlation between circ_0001658 and clinicopathologic characteristics of OS patients. CCK8 assay, colony formation assay, flow cytometry, and transwell assay were performed to determine the function of circ_0001658. Moreover, dualluciferase reporter gene assay was done to verify the targeting relationship between circ_0001658 and miR-382-5p. Compared with adjacent tissues, circ_0001658 displayed a significantly higher expression in OS tissues. Circ_0001658 could facilitate the proliferation, migration, and invasion of OS cells and impede apoptosis by sponging miR-382-5p. Further, circ_0001658 was proved to directly and negatively regulate the expression of miR-382-5 while positively modulate the expression of YB-1. Circ_0001658 promotes the proliferation and metastasis of OS cells via modulating miR-382-5p/YB-1 axis. Significance of the study:In recent years, the expression and function of circular RNA in cancer have been the focus of tumour research. The study on circular RNA helps elucidate the molecular pathology of tumorigenesis and cancer progression.This study demonstrated that circ_0001658 promotes the proliferation and metastasis of OS cells via modulating miR-382-5p/YB-1 axis. To our best knowledge, this work is the first to study the expression and function of circ_0001658 in cancer. K E Y W O R D Scirc_0001658, miR-382-5p, osteosarcoma, YB-1 | INTRODUCTIONOsteosarcoma (OS) is a common primary malignant bone tumour among children and adolescents, frequently diagnosed in the distal femur, the proximal tibia, and the proximal humerus. 1,2 Though multiple treatments offer symptomatic relief and modest improvement in survival for OS patients, the long-term disease-free survival rate of patients remains unfavourable, only 60% to 75%. 3,4 To make matters worse, the 5-year survival rate was only 27% to 55% in patients with local relapsing and distant metastasis treated by the available therapy clinically. 5 Hence, it is imperative to probe into the detailed mechanism of OS.Circular RNA (circRNA) is a novel class of endogenous noncoding RNA, which exists widely and stably in mammalian cells without the function of encoding proteins. 6,7 Circ-RNA, unlike linear RNAs, features a closed-loop structure. 8 This distinctive structure contributes

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Section: Discussionmentioning

confidence: 93%

Circ_0001658 promotes the proliferation and metastasis of osteosarcoma cells via regulating miR‐382‐5p/YB‐1 axis

Wang

et al. 2019

Cell Biochemistry & Function

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“…In order to better understand the genetic mechanisms of progression and evolution in HGOS, matched primary and normal samples from 13 pediatric patients with HGOS and matched metastatic or local recurrence samples of the same patients were analyzed by whole-genome sequencing and integrative analysis [13]. The data confirmed a highly heterogeneous mutational landscape including the presence of hypermutation and microsatellite instability.…”

Section: Somatic Geneticsmentioning

confidence: 97%

“…Given that HGOS has an average of 1.2 mutations per megabase, approximately 1000 samples are needed to obtain a complete catalog of the driver genes of intermediate frequencies. Results and their possible implications for the clinics have recently been reviewed and discussed [8,13].…”

Section: Somatic Geneticsmentioning

confidence: 99%

Genomics and Therapeutic Vulnerabilities of Primary Bone Tumors

Scotlandi

Hattinger

Pellegrini

et al. 2020

Cells

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Osteosarcoma, Ewing sarcoma and chondrosarcoma are rare diseases but the most common primary tumors of bone. The genes directly involved in the sarcomagenesis, tumor progression and treatment responsiveness are not completely defined for these tumors, and the powerful discovery of genetic analysis is highly warranted in the view of improving the therapy and cure of patients. The review summarizes recent advances concerning the molecular and genetic background of these three neoplasms and, of their most common variants, highlights the putative therapeutic targets and the clinical trials that are presently active, and notes the fundamental issues that remain unanswered. In the era of personalized medicine, the rarity of sarcomas may not be the major obstacle, provided that each patient is studied extensively according to a road map that combines emerging genomic and functional approaches toward the selection of novel therapeutic strategies.

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“…Among these, osteosarcoma (OS) is one of the cancer with highest mortality rate in the pediatric population [1]. In the last 35 years, there was no signi cant improvement in the ve-year survival rate if metastases are present during diagnosis [2,3]. Similar to the observation in other cancers, metastasis is a major factor for most death (75%) of OS patients [4].…”

Section: Introductionmentioning

confidence: 95%

Identification and Characterization of Metastasis-Associated Individualized Gene Expression Signature in Osteosarcoma

Zhu

Jin

Zhou

et al. 2020

Preprint

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Background: Osteosarcoma (OS) patients with surgical resection still relapse with poor prognosis due to the inability to detect distant metastasis. It’s essential to identify metastasis-related biomarkers for OS. Methods: Here, a computational pipeline follow relative expression orderings (REOs) using gene expression was constructed in metastases and non-metastases OS patients. Results: 138 metastasis-associated gene pair signatures (MGPSs) were identified follow two independent datasets. A metastases-specific co-expressed MGPS network was constructed for extracting biomarker for clinical application. MGPS such as MYL5 and RPL27A showed strong positive correlation (Cor =0.75, P <0.001). There were thirteen prognostic MGPSs in above network. These prognostic MGPSs could become as a specific classifier to distinguish metastases and non-metastases OS patients. MGPSs were associated with cancer metastasis-related functions. Drug and MGPS network could provide some drug candidates for treatment of OS. Conclusions: Collectively, the roles of the MGPSs in OS were elucidated, which could be beneficial for understanding OS pathogenesis and treatment.

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Integrative genomic analysis of matched primary and metastatic pediatric osteosarcoma

Cited by 44 publications

References 71 publications

Circ_0001658 promotes the proliferation and metastasis of osteosarcoma cells via regulating miR‐382‐5p/YB‐1 axis

Circ_0001658 promotes the proliferation and metastasis of osteosarcoma cells via regulating miR‐382‐5p/YB‐1 axis

Genomics and Therapeutic Vulnerabilities of Primary Bone Tumors

Identification and Characterization of Metastasis-Associated Individualized Gene Expression Signature in Osteosarcoma

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