Circulating miR34a levels as a potential biomarker in the follow-up of Ewing sarcoma
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RESEARCH ARTICLE
Circulating miR34a levels as a potential biomarker in the follow-up of Ewing sarcoma Marika Sciandra 1 & Alessandra De Feo 1 & Alessandro Parra 1 & Lorena Landuzzi 1 & Pier-Luigi Lollini 2 & Maria Cristina Manara 1 & Gianfranco Mattia 3 & Giada Pontecorvi 3 & Cristina Baricordi 1 & Clara Guerzoni 1 & Alberto Bazzocchi 4 & Alessandra Longhi 5 & Katia Scotlandi 1 Received: 6 March 2020 / Accepted: 24 April 2020 # The International CCN Society 2020
Abstract Appropriate tools for monitoring sarcoma progression are still limited. The aim of the present study was to investigate the value of miR-34a-5p (miR34a) as a circulating biomarker to follow disease progression and measure the therapeutic response. Stable forced re-expression of miR34a in Ewing sarcoma (EWS) cells significantly limited tumor growth in mice. Absolute quantification of miR34a in the plasma of mice and 31 patients showed that high levels of this miRNA inversely correlated with tumor volume. In addition, miR34a expression was higher in the blood of localized EWS patients than in the blood of metastatic EWS patients. In 12 patients, we followed miR34a expression during preoperative chemotherapy. While there was no variation in the blood miR34a levels in metastatic patients at the time of diagnosis or after the last cycle of preoperative chemotherapy, there was an increase in the circulating miR34a levels in patients with localized tumors. The three patients with the highest fold-increase in the miR levels did not show evidence of metastasis. Although this analysis should be extended to a larger cohort of patients, these findings imply that detection of the miR34a levels in the blood of EWS patients may assist with the clinical management of EWS. Keywords Ewing sarcoma . miRNAs . miR34a . Circulating biomarkers . Metastases
Marika Sciandra and Alessandra De Feo contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12079-020-00567-2) contains supplementary material, which is available to authorized users. * Alessandra De Feo [email protected]
Gianfranco Mattia [email protected]
* Katia Scotlandi [email protected]
Giada Pontecorvi [email protected]
Marika Sciandra [email protected] Alessandro Parra [email protected] Lorena Landuzzi [email protected] Pier-Luigi Lollini [email protected] Maria Cristina Manara [email protected]
Cristina Baricordi [email protected] Clara Guerzoni [email protected] Alberto Bazzocchi [email protected] Alessandra Longhi [email protected] Extended author information available on the last page of the article
Sciandra M. et al.
Abbreviations EWS Ewing sarcoma miR34a miR-34a-5p ctDNA circulating tumor DNA FBS fetal bovine serum STR short tandem repeat GFP green fluorescence protein pMIF-EV empty lentiviral vector DXR doxorubicin VCR vincristine NSG NOD/SCID gamma s.c. subcutaneously IHC immunohistochemistry ISH in situ miRNA hybridization RT-qPCR qua
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