Predictive Value of micro-RNA Expression Profiling in Pediatric Desmoid Fibromatosis

Background: Lack of clinical predictors of desmoid fibromatosis (DF) outcome highlight the need for biological markers to anticipate DF behavior. In this study we assessed micro-RNA expression profiles in a cohort of children with DF and correlated these findings with patient outcomes aiming to detect predictors of DF outcome.Procedure: A retrospective analysis of 40 DF patients treated at the Children Cancer Hospital Egypt from January 2007 to December 2016 was carried out. Based on initial treatment approach, patients were categorized into three groups. Upfront excision was performed in 14 patients (35%). Nine patients (23%) were subjected only for careful observation while 17 patients (43%) received upfront metronomic chemotherapy. Tumor samples underwent micro-RNA expression analysis. Both unsupervised analysis as well as predictive supervised analysis was performed for the entire cohort.Results: Median time to progression was 71.7, 26.9 and 8.7 months for observation group, chemotherapy and upfront surgery respectively with P = 0.002. Among the nine untreated patients (observation group), four (44%) of them progressed which was strongly correlated with downregulation of miR-378a-5p & hsa-miR-133a-3p, Padj < 0.05. Extremity site was the location for 23 patients, 15 (65%) of them experienced progression. Three downregulated miRNAs hsa-miR-378a-3p, hsa-miR-1-3p and hsa-miR-451a were differentially expressed for those with disease progression, Padj < 0.05.

背景：韧带样型纤维瘤病（desmoid fibromatosis, DF）的临床转归预测因子匮乏，凸显了挖掘生物学标志物以预判DF疾病行为的迫切需求。本研究针对一组儿童DF患者队列的微小RNA（micro-RNA）表达谱进行检测，并将检测结果与患者临床转归相关联，以期筛选出可预测DF转归的标志物。
方法：对2007年1月至2016年12月间在埃及儿童癌症医院接受治疗的40例DF患者开展回顾性分析。根据初始治疗方案，将患者分为三组：14例（35%）接受初始切除术；9例（23%）仅接受密切随访观察；17例（43%）接受初始节拍化疗。对所有患者的肿瘤样本进行微小RNA表达谱检测，并对整组队列分别开展无监督分析与预测性有监督分析。
结果：观察组、化疗组与初始手术组的中位进展时间分别为71.7个月、26.9个月与8.7个月（P=0.002）。在9例仅接受观察的未治疗患者中，4例（44%）出现疾病进展，该进展情况与miR-378a-5p及hsa-miR-133a-3p的下调显著相关（校正后P值<0.05）。23例患者的肿瘤原发部位为肢体，其中15例（65%）出现疾病进展；出现疾病进展的患者中，hsa-miR-378a-3p、hsa-miR-1-3p与hsa-miR-451a这3种微小RNA呈现差异下调表达（校正后P值<0.05）。