Suppressed miR-128-3p combined with TERT overexpression predicts dismal outcomes for neuroblastoma.

IF 1.9 4区医学 Q3 ONCOLOGY Cancer Biomarkers Pub Date : 2022-01-01 DOI:10.3233/CBM-210414

A E Druy, G A Tsaur, E V Shorikov, G A M Tytgat, L G Fechina

{"title":"Suppressed miR-128-3p combined with TERT overexpression predicts dismal outcomes for neuroblastoma.","authors":"A E Druy, G A Tsaur, E V Shorikov, G A M Tytgat, L G Fechina","doi":"10.3233/CBM-210414","DOIUrl":null,"url":null,"abstract":"Background: Molecular and clinical diversity of neuroblastomas is notorious. The activating TERT rearrangements have been associated with dismal prognosis. Suppression of miR-128-3p may complement and enhance the adverse effects of TERT overexpression.Objective: The study aimed at evaluation of prognostic significance of the miR-128-3p/TERT expression in patients with primary neuroblastoma.Methods: RNA samples isolated from fresh-frozen tumor specimens (n= 103) were reverse transcribed for evaluation of miR-128-3p and TERT expression by qPCR. The normalized expression levels were tested for correlations with the event-free survival (EFS). ROC-analysis was used to establish threshold expression levels (TLs) for the possible best prediction of the outcomes. The median follow-up was 57 months.Results: Both TERT overexpression and miR-128-3p downregulation were independently associated with superior rates of adverse events (p= 0.027, TL =-2.32 log10 and p= 0.080, TL =-1.33 log10, respectively). The MYCN single-copy patients were stratified into groups based on the character of alterations in expression of the studied transcripts. Five-year EFS in the groups of patients with elevated TERT/normal miR-128-3p expression and normal TERT/reduced miR-128-3p expression were 0.74 ± 0.08 and 0.60 ± 0.16, respectively. The patients with elevated TERT/reduced miR-128-3p expression had the worst outcomes, with 5-year EFS of 0.40 ± 0.16 compared with 0.91 ± 0.06 for the patients with unaltered levels of both transcripts (p< 0.001). Cumulative incidence of relapse/progression for the groups constituted 0.23 ± 0.08, 0.40 ± 0.16, 0.60 ± 0.16 and 0.09 ± 0.06, respectively. Moreover, the loss of miR-128-3p was qualified as independent adverse predictor which outperformed the conventional clinical and genetic risk factors in the multivariate Cox regression model of EFS.Conclusions: Combined expression levels of miR-128-3p and TERT represent a novel prognostic biomarker for neuroblastoma.","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":"13 1","pages":"661-671"},"PeriodicalIF":1.9000,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Biomarkers","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3233/CBM-210414","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Molecular and clinical diversity of neuroblastomas is notorious. The activating TERT rearrangements have been associated with dismal prognosis. Suppression of miR-128-3p may complement and enhance the adverse effects of TERT overexpression.

Objective: The study aimed at evaluation of prognostic significance of the miR-128-3p/TERT expression in patients with primary neuroblastoma.

Methods: RNA samples isolated from fresh-frozen tumor specimens (n= 103) were reverse transcribed for evaluation of miR-128-3p and TERT expression by qPCR. The normalized expression levels were tested for correlations with the event-free survival (EFS). ROC-analysis was used to establish threshold expression levels (TLs) for the possible best prediction of the outcomes. The median follow-up was 57 months.

Results: Both TERT overexpression and miR-128-3p downregulation were independently associated with superior rates of adverse events (p= 0.027, TL =-2.32 log10 and p= 0.080, TL =-1.33 log10, respectively). The MYCN single-copy patients were stratified into groups based on the character of alterations in expression of the studied transcripts. Five-year EFS in the groups of patients with elevated TERT/normal miR-128-3p expression and normal TERT/reduced miR-128-3p expression were 0.74 ± 0.08 and 0.60 ± 0.16, respectively. The patients with elevated TERT/reduced miR-128-3p expression had the worst outcomes, with 5-year EFS of 0.40 ± 0.16 compared with 0.91 ± 0.06 for the patients with unaltered levels of both transcripts (p< 0.001). Cumulative incidence of relapse/progression for the groups constituted 0.23 ± 0.08, 0.40 ± 0.16, 0.60 ± 0.16 and 0.09 ± 0.06, respectively. Moreover, the loss of miR-128-3p was qualified as independent adverse predictor which outperformed the conventional clinical and genetic risk factors in the multivariate Cox regression model of EFS.

Conclusions: Combined expression levels of miR-128-3p and TERT represent a novel prognostic biomarker for neuroblastoma.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

抑制miR-128-3p联合TERT过表达可预测神经母细胞瘤的预后。

背景：神经母细胞瘤的分子和临床多样性是众所周知的。激活TERT重排与预后不良有关。抑制miR-128-3p可能会补充并增强TERT过表达的不良影响。目的：探讨miR-128-3p/TERT表达在原发性神经母细胞瘤患者中的预后意义。方法：从新鲜冷冻肿瘤标本（n= 103）中分离RNA样本，用qPCR方法逆转录miR-128-3p和TERT表达。检测标准化表达水平与无事件生存期（EFS）的相关性。roc分析用于建立阈值表达水平（TLs），以便可能最好地预测结果。中位随访时间为57个月。结果：TERT过表达和miR-128-3p下调均与不良事件发生率较高独立相关（p= 0.027, TL =-2.32 log10; p= 0.080, TL =-1.33 log10）。根据所研究转录本表达改变的特征，将MYCN单拷贝患者分层。TERT/ miR-128-3p表达升高组和TERT正常/ miR-128-3p表达降低组的5年EFS分别为0.74±0.08和0.60±0.16。TERT升高/ miR-128-3p表达降低的患者预后最差，5年EFS为0.40±0.16，而两种转录物水平不变的患者为0.91±0.06 （p< 0.001）。两组复发/进展累积发生率分别为0.23±0.08、0.40±0.16、0.60±0.16和0.09±0.06。此外，在EFS的多变量Cox回归模型中，miR-128-3p的缺失可以作为独立的不良预测因素，优于传统的临床和遗传危险因素。结论：miR-128-3p和TERT的联合表达水平代表了一种新的神经母细胞瘤预后生物标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Cancer Biomarkers ONCOLOGY-

CiteScore

5.20

自引率

3.20%

发文量

195

审稿时长

3 months

期刊介绍： Concentrating on molecular biomarkers in cancer research, Cancer Biomarkers publishes original research findings (and reviews solicited by the editor) on the subject of the identification of markers associated with the disease processes whether or not they are an integral part of the pathological lesion. The disease markers may include, but are not limited to, genomic, epigenomic, proteomics, cellular and morphologic, and genetic factors predisposing to the disease or indicating the occurrence of the disease. Manuscripts on these factors or biomarkers, either in altered forms, abnormal concentrations or with abnormal tissue distribution leading to disease causation will be accepted.