Non-Coding RNAs as Prognostic Biomarkers: A miRNA Signature Specific for Aggressive Early-Stage Lung Adenocarcinomas.
Non-Coding RNAs as Prognostic Biomarkers: A miRNA Signature Specific for Aggressive Early-Stage Lung Adenocarcinomas.
复制标题
DOI：
10.3390/ncrna6040048
复制
发表时间：
2020-12-15
期刊：
影响因子：
4.3
通讯作者：
Bianchi F
中科院分区：
文献类型：
--
作者：
Dama E;Melocchi V;Mazzarelli F;Colangelo T;Cuttano R;Di Candia L;Ferretti GM;Taurchini M;Graziano P;Bianchi F
肺癌负担可以通过采取一级和二级预防策略来降低，如反吸烟运动和对高危受试者（年龄>50岁和吸烟者>30包/年）进行低剂量CT筛查。最近的CT筛查试验表明，向早期肺癌的阶段转移和死亡率降低（约20%）。然而，相当一部分患有早期疾病的患者（30-50%）仍然经历复发和不良预后。因此，在I期肺癌中鉴定有效的预后生物标志物是当今最重要的。在这里，我们应用了一种多层次的方法，依赖于一个大型肺癌患者队列（TCGA-LUAD，n = 510）的耦合RNA-seq和miRNA-seq数据分析，这使我们能够识别I期肺腺癌中的预后miRNA特征。这些特征在侵袭性疾病评分中显示出高准确性（AUC范围在0.79和0.85之间）。重要的是，使用基于网络的方法，我们重新连接了miRNA-mRNA调控网络，鉴定了7种miRNAs的最小签名，其在FFPE肺腺癌样本（CSS，n = 44）的队列中得到验证，并控制了与癌症相关通路重叠的多种基因。我们的研究结果进一步证明了基于miRNA的生物标志物用于肺癌诊断的可靠性，并使miRNA生物标志物在临床常规中的应用向前迈进了一步。
Lung cancer burden can be reduced by adopting primary and secondary prevention strategies such as anti-smoking campaigns and low-dose CT screening for high risk subjects (aged >50 and smokers >30 packs/year). Recent CT screening trials demonstrated a stage-shift towards earlier stage lung cancer and reduction of mortality (~20%). However, a sizable fraction of patients (30–50%) with early stage disease still experience relapse and an adverse prognosis. Thus, the identification of effective prognostic biomarkers in stage I lung cancer is nowadays paramount. Here, we applied a multi-tiered approach relying on coupled RNA-seq and miRNA-seq data analysis of a large cohort of lung cancer patients (TCGA-LUAD, n = 510), which enabled us to identify prognostic miRNA signatures in stage I lung adenocarcinoma. Such signatures showed high accuracy (AUC ranging between 0.79 and 0.85) in scoring aggressive disease. Importantly, using a network-based approach we rewired miRNA-mRNA regulatory networks, identifying a minimal signature of 7 miRNAs, which was validated in a cohort of FFPE lung adenocarcinoma samples (CSS, n = 44) and controls a variety of genes overlapping with cancer relevant pathways. Our results further demonstrate the reliability of miRNA-based biomarkers for lung cancer prognostication and make a step forward to the application of miRNA biomarkers in the clinical routine.