Sciandra Marika, De Feo Alessandra, Parra Alessandro, Landuzzi Lorena, Lollini Pier-Luigi, Manara Maria Cristina, Mattia Gianfranco, Pontecorvi Giada, Baricordi Cristina, Guerzoni Clara, Bazzocchi Alberto, Longhi Alessandra, Scotlandi Katia
Laboratory of Experimental Oncology, IRCCS Istituto Ortopedico Rizzoli, via di Barbiano 1/10, 40136, Bologna, Italy.
Department of Experimental, Diagnostic and Specialty Medicine, DIMES, University of Bologna, Bologna, Italy.
J Cell Commun Signal. 2020 Sep;14(3):335-347. doi: 10.1007/s12079-020-00567-2. Epub 2020 Jun 5.
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.
用于监测肉瘤进展的合适工具仍然有限。本研究的目的是探讨miR-34a-5p（miR34a）作为循环生物标志物在跟踪疾病进展和评估治疗反应方面的价值。在尤因肉瘤（EWS）细胞中稳定强制重新表达miR34a可显著限制小鼠肿瘤生长。对小鼠和31例患者血浆中miR34a的绝对定量分析表明，该miRNA的高水平与肿瘤体积呈负相关。此外，局限性EWS患者血液中的miR34a表达高于转移性EWS患者。在12例患者中，我们在术前化疗期间跟踪miR34a的表达。转移性患者在诊断时或术前化疗最后一个周期后血液中miR34a水平没有变化，而局限性肿瘤患者循环miR34a水平有所升高。miR水平升高倍数最高的3例患者未显示转移迹象。尽管该分析应扩展至更大规模的患者队列，但这些发现表明，检测EWS患者血液中的miR34a水平可能有助于EWS的临床管理。
