Mairinger Fabian Dominik, Ting Saskia, Werner Robert, Walter Robert Fred Henry, Hager Thomas, Vollbrecht Claudia, Christoph Daniel, Worm Karl, Mairinger Thomas, Sheu-Grabellus Sien-Yi, Theegarten Dirk, Schmid Kurt Werner, Wohlschlaeger Jeremias
Institute of Pathology and Neuropathology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
1] Institute of Pathology and Neuropathology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany [2] Department of interventional Pneumology, Ruhrlandklinik, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Mod Pathol. 2014 Dec;27(12):1632-40. doi: 10.1038/modpathol.2014.74. Epub 2014 May 30.
MicroRNAs (miRNAs) are a class of small (∼22 nucleotides), non-coding, highly conserved single-stranded RNAs with posttranscriptional regulatory features, including the regulation of cell proliferation, differentiation, survival, and apoptosis. They are deregulated in a broad variety of tumors showing characteristic expression patterns and can, thus, be used as a diagnostic tool. In contrast to non-small cell carcinoma of the lung neuroendocrine lung tumors, encompassing typical and atypical carcinoids, small cell lung cancer and large cell neuroendocrine lung cancer, no data about deregulation of tumor entity-specific miRNAs are available to date. miRNA expression differences might give useful information about the biological characteristics of these tumors, as well as serve as helpful markers.In 12 pulmonary neuroendocrine tumors classified as either typical carcinoid, atypical, large cell neuroendocrine or small cell lung cancer, screening for 763 miRNAs known to be involved in pulmonary cancerogenesis was conducted by performing 384-well TaqMan low-density array real-time qPCR. In the entire cohort, 44 miRNAs were identified, which showed a significantly different miRNA expression. For 12 miRNAs, the difference was highly significant (P<0.01). Eight miRNAs showed a negative (miR-22, miR-29a, miR-29b, miR-29c, miR-367*; miR-504, miR-513C, miR-1200) and four miRNAs a positive (miR-18a, miR-15b*, miR-335*, miR-1201) correlation to the grade of tumor biology. The miRNAs let-7d; miR-19; miR-576-5p; miR-340*; miR-1286 are significantly associated with survival. Members of the miR-29 family seem to be extremely important in this group of tumors. We found a number of miRNAs, which showed a highly significant deregulation in pulmonary neuroendocrine tumors. Moreover, some of these deregulated miRNAs seem to allow discrimination of the various subtypes of pulmonary neuroendocrine tumors. Thus, the analysis of specific sets of miRNAs can be proposed as diagnostic and/or predictive markers in this group of neoplasias.
微小RNA（miRNA）是一类小的（约22个核苷酸）、非编码、高度保守的单链RNA，具有转录后调控功能，包括对细胞增殖、分化、存活和凋亡的调控。它们在多种肿瘤中表达失调，呈现出特征性的表达模式，因此可作为一种诊断工具。与肺非小细胞癌不同，肺神经内分泌肿瘤包括典型类癌、非典型类癌、小细胞肺癌和大细胞神经内分泌肺癌，目前尚无关于肿瘤实体特异性miRNA表达失调的数据。miRNA表达差异可能为这些肿瘤的生物学特性提供有用信息，也可作为有用的标志物。在12例分类为典型类癌、非典型类癌、大细胞神经内分泌癌或小细胞肺癌的肺神经内分泌肿瘤中，通过进行384孔TaqMan低密度阵列实时定量PCR，对已知参与肺癌发生的763种miRNA进行筛查。在整个队列中，鉴定出44种miRNA，其miRNA表达存在显著差异。对于12种miRNA，差异非常显著（P<0.01）。8种miRNA（miR-22、miR-29a、miR-29b、miR-29c、miR-367*；miR-504、miR-513C、miR-1200）与肿瘤生物学分级呈负相关，4种miRNA（miR-18a、miR-15b*、miR-335*、miR-1201）与肿瘤生物学分级呈正相关。miRNA let-7d；miR-19；miR-576-5p；miR-340*；miR-1286与生存显著相关。miR-29家族成员在这组肿瘤中似乎极为重要。我们发现了一些在肺神经内分泌肿瘤中表达高度失调的miRNA。此外，其中一些失调的miRNA似乎能够区分肺神经内分泌肿瘤的不同亚型。因此，对特定miRNA组的分析可作为这组肿瘤的诊断和/或预测标志物。
