Rapa Ida, Votta Arianna, Felice Barbara, Righi Luisella, Giorcelli Jessica, Scarpa Aldo, Speel Ernst-Jan M, Scagliotti Giorgio V, Papotti Mauro, Volante Marco
Department of Oncology, San Luigi Hospital, University of Turin, Orbassano, Italy.
Neuroendocrinology. 2015;101(3):246-55. doi: 10.1159/000381454. Epub 2015 Mar 16.
To extensively explore microRNA expression profiles in lung carcinoids in correlation with clinical and pathological features.
A PCR-based array was employed in the screening phase to analyze 752 microRNAs in a discovery set of 12 lung carcinoids, including 6 typical (3 with lymph node metastasis) and 6 atypical (3 with lymph node metastasis). The results were validated by means of real-time PCR in 37 carcinoids, including 22 typical (4 with lymph node metastasis) and 15 atypical (7 with lymph node metastasis), and 19 high-grade neuroendocrine carcinomas.
Unsupervised cluster analysis segregated the pilot cases into 3 distinct groups. Twenty-four microRNAs were differentially regulated in atypical versus typical carcinoids, and 29 in metastatic versus nonmetastatic cases. Eleven microRNAs were selected for validation. All but 1 were significantly different among lung neuroendocrine tumor histotypes. Moreover, 5 (miR-129-5p, miR-409-3p, miR-409-5p, miR-185 and miR-497) were significantly upregulated in typical compared to atypical carcinoids. MiR-409-3p, miR-409-5p and miR-431-5p were also significantly downregulated in carcinoids metastatic to the lymph nodes. Predictive in silico analysis of specific target genes showed that these 3 latter microRNAs linked to metastatic potential are implicated in several cellular functions and highlighted several novel genes which may be worth exploring.
Our findings demonstrate that lung carcinoids have distinct microRNA expression profiles as compared to high-grade neuroendocrine carcinomas and that specific microRNAs might have potential implications as diagnostic tools or clinical biomarkers.
广泛探究肺类癌中的微小RNA表达谱及其与临床和病理特征的相关性。
在筛选阶段采用基于聚合酶链反应的芯片分析12例肺类癌（包括6例典型类癌，其中3例有淋巴结转移；6例非典型类癌，其中3例有淋巴结转移）中的752种微小RNA。通过实时聚合酶链反应在37例类癌（包括22例典型类癌，其中4例有淋巴结转移；15例非典型类癌，其中7例有淋巴结转移）和19例高级别神经内分泌癌中验证结果。
无监督聚类分析将试点病例分为3个不同组。24种微小RNA在非典型类癌与典型类癌中差异表达，29种在有转移与无转移病例中差异表达。选择11种微小RNA进行验证。除1种外，所有微小RNA在肺神经内分泌肿瘤组织学类型之间均有显著差异。此外，与非典型类癌相比，5种微小RNA（miR-129-5p、miR-409-3p、miR-409-5p、miR-185和miR-497）在典型类癌中显著上调。miR-409-3p、miR-409-5p和miR-431-5p在发生淋巴结转移的类癌中也显著下调。对特定靶基因的计算机预测分析表明，这3种与转移潜能相关的微小RNA涉及多种细胞功能，并突出了几个可能值得探索的新基因。
我们的研究结果表明，与高级别神经内分泌癌相比，肺类癌具有独特的微小RNA表达谱，特定的微小RNA可能作为诊断工具或临床生物标志物具有潜在意义。
