Giordano Mirella, Boldrini Laura, Servadio Adele, Niccoli Cristina, Melfi Franca, Lucchi Marco, Mussi Alfredo, Fontanini Gabriella
Department of Surgical, Medical, Molecular Pathology and Critical Area, University of PisaPisa 56126, Italy.
Am J Transl Res. 2018 Mar 15;10(3):892-900. eCollection 2018.
Lung cancer is the leading cause of cancer-related mortality, and approximately 80% of cases are non-small cell lung cancer (NSCLC). Recently, the incidence of NSCLC has been quickly increasing, while the age of patients at diagnosis is decreasing. To date, it is still controversial whether younger patients have better or worse outcomes compared with their older counterparts. MicroRNAs (miRNAs) have been defined to play a key role in cancer pathogenesis, and their aberrant expression has been suggested as a potential biomarker of prognosis in lung adenocarcinoma. To understand the molecular features of young and old adenocarcinoma patients, we investigated the expression level of a panel of miRNAs selected after a mini-literature review. The expression analysis was performed by the nCounter System® (NanoString Technologies) directly on RNA, including small RNAs. The analysis revealed that 7 miRNAs (miR-25-3p, miR-29c-3p, miR-33a-5p, miR-144-3p, miR-153-3p, miR-342-5p and miR-485-3p) were differentially expressed in the two groups (<0.05). All of these miRNAs showed higher expression levels in young compared to old patients, and their predicted targets included and Ra. miR-144-3p had an opposite influence on overall survival since its upregulation was associated with a worse prognosis in young patients (=0.01) and with a better outcome in the older group (=0.03). We observed that lung cancer in young and old patients may be influenced by different regulatory mechanisms. Moreover, one of the down-regulated miRNAs showed a different prognostic impact in the two groups, confirming that young and old patients deserve a specific clinical approach.
肺癌是癌症相关死亡的主要原因,约80%的病例为非小细胞肺癌(NSCLC)。近年来,NSCLC的发病率迅速上升,而患者的诊断年龄却在下降。迄今为止,与老年患者相比,年轻患者的预后是更好还是更差仍存在争议。微小RNA(miRNA)在癌症发病机制中起着关键作用,其异常表达被认为是肺腺癌预后的潜在生物标志物。为了解年轻和老年腺癌患者的分子特征,我们在进行了小型文献综述后,研究了一组miRNA的表达水平。通过nCounter System®(NanoString Technologies)直接对包括小RNA在内的RNA进行表达分析。分析显示,7种miRNA(miR-25-3p、miR-29c-3p、miR-33a-5p、miR-144-3p、miR-153-3p、miR-342-5p和miR-485-3p)在两组中的表达存在差异(<0.05)。与老年患者相比,所有这些miRNA在年轻患者中的表达水平更高,其预测靶点包括 和Ra。miR-144-3p对总生存期有相反的影响,因为其上调与年轻患者较差的预后相关(=0.01),而在老年组中则与较好的预后相关(=0.03)。我们观察到,年轻和老年患者的肺癌可能受不同调节机制的影响。此外,一种下调的miRNA在两组中显示出不同的预后影响,这证实了年轻和老年患者需要特定的临床治疗方法。