Loss of MTAP Expression is a Negative Prognostic Marker in Ewing Sarcoma Family of Tumors

Abrahão-Machado, Lucas Faria; Antunes, Bruno Pereira; Filippi, Renée Zon; Volc, Sáhlua Miguel; Boldrini, Érica; Menezes, Weder Pereira de; Reis, Rui Manuel; Camargo, Olavo Pires de

doi:10.2217/bmm-2017-0152

Cited by 9 publications

(3 citation statements)

References 19 publications

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“…Others: Machado et al found that when MTAP expression was lost in ES, the overall survival was shorter [53] . Naranjo et al found that high ERBB4 expression is associated with metastatic disease in ES patient samples [54] .…”

Section: Resultsmentioning

confidence: 99%

Molecular and biologic biomarkers of Ewing sarcoma: A systematic review

Daher¹,

Zalaquett²,

Chalhoub³

et al. 2023

Journal of Bone Oncology

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Section: Resultsmentioning

confidence: 99%

Molecular and biologic biomarkers of Ewing sarcoma: A systematic review

Daher¹,

Zalaquett²,

Chalhoub³

et al. 2023

Journal of Bone Oncology

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“… 4 Therefore, researchers are paying more and more attention to the predictive function of characteristic molecular markers for EWS patient prognosis. The existing studies have examined the expression of genes, such as SOX2, MTAP, and Connexin, and their relationship to outcomes in patients with EWS, 21 , 22 , 23 yet no clinically available marker or an actual target for therapy has emerged from those investigations. One of the goals in EWS treatment is to find prognostic or predictive biomarkers that will be able to guide therapeutic decisions and serve as targets for novel therapies.…”

Section: Discussionmentioning

confidence: 99%

Suggested role for neutrophil extracellular trap formation in Ewing sarcoma immune microenvironment

Shukrun,

Baron,

Fidel

et al. 2023

Cancer Science

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Ewing sarcoma (EWS) is a highly aggressive cancer with a survival rate of 70%–80% for patients with localized disease and under 30% for those with metastatic disease. Tumor‐infiltrating neutrophils (TIN) can generate extracellular net‐like DNA structures known as neutrophil extracellular traps (NETs). However, little is known about the presence and prognostic significance of tumor‐infiltrating NETs in EWS. Herein, we investigated 46 patients diagnosed with EWS and treated in the Tel Aviv Medical Center between 2010 and 2021. TINs and NETs were identified in diagnostic biopsies of EWS by immunofluorescence. In addition, NETs were investigated in neutrophils isolated from peripheral blood samples of EWS patients at diagnosis and following neoadjuvant chemotherapy. The relationships between the presence of TINs and NETs, pathological and clinical features, and outcomes were analyzed. Our results demonstrate that TIN and NETs at diagnosis were higher in EWS patients with metastatic disease compared with those with local disease. High NET formation at diagnosis predicted poor response to neoadjuvant chemotherapy, relapse, and death from disease (p < 0.05). NET formation in peripheral blood samples at diagnosis was significantly elevated among patients with EWS compared with pediatric controls and decreased significantly following neoadjuvant chemotherapy. In conclusion, NET formation seems to have a role in the EWS immune microenvironment. Their presence can refine risk stratification, predict chemotherapy resistance and survival, and serve as a therapeutic target in patients with EWS.

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“…For pediatric gliomas, MTAP were more frequent in grade IV gliomas (62.5%, p = 0.0087) but rare in grade I gliomas (12.2%, p = 0.0178); besides, MTAP gene deletion was correlated with a poor survival (p = 0.01) and a shorter PFS (p = 0.016) 26 . The results from the Ewing sarcoma family of tumors also revealed loss of MTAP expression was a negative prognostic marker 27 . The present study was consistent with previous studies, that the shorter survival (p = 0.044) and PFS (p = 0.002) were in patients with MTAP low expression, even though they were more sensitive to pemetrexed than patients with MTAP high expression.…”

Section: Variablesmentioning

confidence: 99%

MTAP-deficiency could predict better treatment response in advanced lung adenocarcinoma patients initially treated with pemetrexed-platinum chemotherapy and bevacizumab

Wang

Zhu

Liu

et al. 2020

Sci Rep

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To investigate the predictive value of methylthioadenosine phosphorylase (MTAP) on treatment response and survival in advanced lung adenocarcinoma. MTAP expression was detected by immunohistochemistry. Treatment response and survival were compared according to MTAP expression level. The results indicated MTAP-low expression was observed in 61.2% (101/165) of all patients. The objective response rate and disease control rate improved in the MTAP-low group (64.4% vs 46.9%, p = 0.035; 92.1% vs. 79.7%, p = 0.03; respectively). The median progression-free survival and survival time in the MTAP-low group were significantly lower than that in the MTAP-high group (8.1 vs. 13.1 months, p = 0.002; 22 vs. 32 months, p = 0.044). Multivariate analysis demonstrated that brain metastasis (HR 1.55, p = 0.046), thoracic radiation (HR 0.52, p = 0.026), and MTAP-low expression (HR 1.36, p = 0.038) were independent factors on survival. It is concluded that MTAP-low expression could predict improved treatment response but worsened survival in advanced lung adenocarcinoma.

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Loss of MTAP Expression is a Negative Prognostic Marker in Ewing Sarcoma Family of Tumors

Abstract: Loss of MTAP expression is an independent negative prognostic biomarker in ESFT.

Cited by 9 publications

References 19 publications

Molecular and biologic biomarkers of Ewing sarcoma: A systematic review

Molecular and biologic biomarkers of Ewing sarcoma: A systematic review

Suggested role for neutrophil extracellular trap formation in Ewing sarcoma immune microenvironment

MTAP-deficiency could predict better treatment response in advanced lung adenocarcinoma patients initially treated with pemetrexed-platinum chemotherapy and bevacizumab

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