Effect of timing of pulmonary metastasis occurrence on the outcome of metastasectomy in osteosarcoma patients

Ahmed, Gehad; Zamzam, Manal; Kamel, Ayman H.; Ahmed, Sonia; Salama, A.E.; Zaki, Iman; Kamal, Nehal; Elshafiey, Maged M.

doi:10.1016/j.jpedsurg.2018.06.019

Cited by 47 publications

(42 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Approximately 50% of all patients at the time of diagnosis develop metastases, which results in a high mortality rate despite improvements in radiotherapy, adjuvant chemotherapy and surgery. [1][2][3] Elucidation of the molecular basis of OS progression is conducive to developing effective therapeutic agents and improving OS patient's prognosis.…”

Section: Introductionmentioning

confidence: 99%

<p>Upregulated lncRNA THRIL/TNF-α Signals Promote Cell Growth and Predict Poor Clinical Outcomes of Osteosarcoma</p>

Xu¹,

Jin²,

Yang³

et al. 2020

OTT

View full text Add to dashboard Cite

Background: The immunosuppressive facet and tumorigenic role of TNF-α have been revealed in osteosarcoma (OS). Long noncoding RNA THRIL is identified to regulate TNF-α expression and participates in immune response. Thus, investigations on the clinical expression pattern of THRIL/TNF-α signal in OS would provide a potential target premise for OS patients. Methods: We collected OS (n=83), nontumor tissues (n=37) and serum samples (n=83 for OS and n=40 for healthy control) to determine the expressions and clinical significance of THRIL/TNF-α signal. Knockdown of THRIL in OS cell lines MG63 and Saos2 in vitro and in vivo was performed to confirm its function in the development of OS. Results: Elevated expression of THRIL was associated with increased TNF-α levels in OS tissues and serum samples. Combination of THRIL and TNF-α in tissues showed a more efficient diagnostic value for OS patients than either of them. Moreover, high-expressed THRIL was associated with larger tumor size, advanced Enneking stage and lung metastasis, whereas high TNF-α expression was found in patients with high histologic grade and patients who simultaneously harbor high THRIL and TNF-α showed the worst overall survival and metastasis-free survival. TNF-α signals increased OS cell vitalities in vitro but knockdown of THRIL inhibited TNF-α expressions, leading to impaired cell vitality, increased apoptosis and also downregulated epithelial to mesenchymal transition (EMT) phenotype and the ability of invasion, but these processes were restored by the treatment of TNF-α. The oncogenic role of THRIL/TNF-α signal was also confirmed in the xenograft model of MG63 cells. Conclusion: Overexpressed THRIL and TNF-α promoted OS progression with efficient diagnostic and prognostic value. THRIL/TNF-α signal supported cell growth and EMT phenotype of OS cells in vitro and in vivo.

show abstract

Section: Introductionmentioning

confidence: 99%

<p>Upregulated lncRNA THRIL/TNF-α Signals Promote Cell Growth and Predict Poor Clinical Outcomes of Osteosarcoma</p>

Xu¹,

Jin²,

Yang³

et al. 2020

OTT

View full text Add to dashboard Cite

show abstract

“…Current clinical treatments are not effective for patients with OS-associated metastasis and recurrence, thus the prognosis of patients with end-stage OS with metastasis has not improved (28). In addition, epidemiological studies have shown that metastasis is the leading cause of death in patients with OS (29). Therefore, exploring the molecular mechanism of OS and discovering novel therapeutic targets has important clinical significance for improving the survival and prognosis of patients with OS.…”

Section: Discussionmentioning

confidence: 99%

Metastasis‑associated gene MAPK15 promotes the migration and invasion of osteosarcoma cells via the c‑Jun/MMPs pathway

Yang

Zeng

et al. 2020

Oncol Lett

View full text Add to dashboard Cite

Osteosarcoma (OS) is the most common and destructive primary bone malignancy to affect children and adolescents. Metastases remain the primary cause of death in patients with OS. In the present study, weight gene co-expressed network analysis (WGCNA) and differentially-expressed gene analysis were used to identify key genes associated with the metastasis of OS. Reverse transcription-quantitative PCR and immunohistochemical staining were then used to detect the expression levels of these key genes in OS tissues, and to determine the hub genes of interest. Wound-healing and transwell assays, in addition to a lung metastasis model, were used to detect the effects of the hub genes on OS cell proliferation and metastasis in vitro and in vivo. Using WGCNA and differential expression analysis, deleted in lung and esophageal cancer protein 1 (DLEC1), Forkhead box J1 (FOXJ1) and mitogen-activated protein kinase 15 (MAPK15) were predicted to be key metastasis-associated genes, and highly expressed in metastatic OS tissues; among them, the protein and mRNA expression levels of MAPK15 were most significantly increased in our OS tissues from patients who exhibited metastases at diagnosis, and thus MAPK15 was determined to be a metastasis-associated hub gene to further study. Furthermore, inhibiting MAPK15 expression significantly decreased OS cell metastasis in vitro and in vivo, as well as suppressing c-Jun/matrix metalloproteinase (MMP)-associated pathways. Overexpression of MAPK15 activated the c-Jun/MMPs pathway and promoted OS cell metastasis, while inhibition of c-Jun blocked this effect. Taken together, MAPK15 was indicated to be an OS metastasis-associated gene, and was confirmed to promote the migration and invasion of OS cells via the c-Jun/MMP pathway. MAPK15 may therefore be an effective target for the treatment of OS.

show abstract

“…OS is a malignant bone tumor with a high incidence in adolescents, while its prognosis is poor due to pulmonary metastasis (25). Accumulating evidence has indicated that miRNAs act as tumor suppressor genes or oncogenes associated with the progression of OS (26,27).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑208a‑3p promotes osteosarcoma progression via targeting PTEN

Wang

et al. 2020

Exp Ther Med

View full text Add to dashboard Cite

Osteosarcoma (OS) is a malignant bone tumor with a poor prognosis. Accumulated evidence has suggested that microRNAs (miRNAs/miRs) may function as either oncogenes or tumor suppressors, which are associated with tumorigenesis and the progression of different types of cancer. In the present study, the role of miR-208a-3p in OS was investigated. The expression levels of miR-208a-3p in OS tissues and cell lines were determined via reverse transcription-quantitative PCR (RT-qPCR). MTT and colony formation assays were performed to verify the proliferation rate of OS cells. In addition, the effects of miR-208a-3p on the migration and invasion of OS cells were revealed using wound-healing and Transwell assays, respectively. Furthermore, the association between miR-208a-3p and phosphatase and tensin homolog (PTEN) 3'-untranslated region was determined via luciferase reporter assays, western blot and RT-qPCR analysis. The results indicated that miR-208a-3p was upregulated in OS tissues and cell lines compared with adjacent normal tissues and human osteoblastic cells, respectively. miR-208a-3p overexpression promoted and miR-208a-3p knockdown inhibited OS cells proliferation and metastatic potential. Additionally, PTEN was validated as a direct target of miR-208a-3p and its expression was negatively associate with that of miR-208a-3p in OS cells. Taken together, these results may suggest that miR-208a-3p promoted OS cells proliferation and metastatic potential via targeting PTEN. Therefore, miR-208a-3p may be considered as a diagnostic biomarker for OS.

show abstract

Effect of timing of pulmonary metastasis occurrence on the outcome of metastasectomy in osteosarcoma patients

Cited by 47 publications

References 16 publications

<p>Upregulated lncRNA THRIL/TNF-α Signals Promote Cell Growth and Predict Poor Clinical Outcomes of Osteosarcoma</p>

<p>Upregulated lncRNA THRIL/TNF-α Signals Promote Cell Growth and Predict Poor Clinical Outcomes of Osteosarcoma</p>

Metastasis‑associated gene MAPK15 promotes the migration and invasion of osteosarcoma cells via the c‑Jun/MMPs pathway

MicroRNA‑208a‑3p promotes osteosarcoma progression via targeting PTEN

Contact Info

Product

Resources

About