Pulmonary neuroendocrine neoplasms (NENs) are classified into low-grade neuroendocrine tumors and high-grade neuroendocrine carcinomas (NECs). There are significant differences in therapeutic strategies of the different NEN subtypes, and therefore, precise classification of pulmonary NENs is critical. However, challenges in pulmonary NEN classification include overlap of diagnostic histological features among the subtypes and reduced or negative expression of neuroendocrine markers in poorly differentiated pulmonary NECs. Recently, transcription factor insulinoma-associated protein 1 (INSM1) was identified as a sensitive marker of neuroendocrine and neuroepithelial differentiation. In this study, INSM1 expression was detected by immunohistochemistry in greater than 94% of pulmonary NENs, indicating that it is a highly sensitive marker of pulmonary NENs and is useful to detect poorly differentiated pulmonary NECs. Although there are well-established morphological and immunohistologic criteria to diagnose pulmonary NENs, there is no universal consensus regarding prognostic markers of pulmonary NENs. Studies have shown that non–small cell lung cancers express long non-coding RNAs (lncRNAs), which regulate gene expression, epithelial-to-mesenchymal transition, and carcinogenesis. We characterized expression and function of lncRNAs, including HOX transcript antisense RNA (HOTAIR), maternally expressed 3 (MEG3), and prostate cancer antigen 3 (PCA3) in pulmonary NENs, including typical carcinoid tumors, atypical carcinoid tumors, small cell lung carcinoma (SCLC/NEC), and large cell neuroendocrine carcinoma (LCNEC/NEC). In situ hybridization and real-time polymerase chain reaction studies showed higher expression (p < 0.01) of all lncRNAs in SCLC/NEC. Small interfering RNA studies indicated a role for MEG3 and PCA3 in tumor proliferation. Therefore, these lncRNAs may serve as prognostic indicators of pulmonary NEN aggressiveness and as possible therapeutic targets.

中文翻译：

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肺神经内分泌肿瘤中的长非编码RNA。

肺神经内分泌肿瘤（NEN）分为低度神经内分泌肿瘤和高度神经内分泌癌（NEC）。不同NEN亚型的治疗策略存在显着差异，因此，肺NEN的精确分类至关重要。但是，肺NEN分类中的挑战包括亚型之间的诊断组织学特征重叠以及低分化肺NEC中神经内分泌标记物的减少或阴性表达。最近，转录因子胰岛素瘤相关蛋白1（INSM1）被确定为神经内分泌和神经上皮分化的敏感标记。在这项研究中，通过免疫组织化学检测到了超过94％的肺NEN中有INSM1表达，表明它是肺NEN的高度敏感标记，可用于检测分化差的肺NEC。尽管有公认的形态学和免疫组织学标准可诊断肺NEN，但关于肺NEN的预后指标尚无共识。研究表明，非小细胞肺癌表达长的非编码RNA（lncRNA），该RNA调节基因表达，上皮向间充质转化以及癌变。我们表征了lncRNA的表达和功能，包括HOX转录反义RNA（研究表明，非小细胞肺癌表达长的非编码RNA（lncRNA），该RNA调节基因表达，上皮向间充质转化以及癌变。我们表征了lncRNA的表达和功能，包括HOX转录反义RNA（研究表明，非小细胞肺癌表达长的非编码RNA（lncRNA），该RNA调节基因表达，上皮向间充质转化以及癌变。我们表征了lncRNA的表达和功能，包括HOX转录反义RNA（HOTAIR），在肺NEN中母体表达3（MEG3）和前列腺癌抗原3（PCA3），包括典型的类癌，非典型类癌，小细胞肺癌（SCLC / NEC）和大细胞神经内分泌癌（LCNEC / NEC） ）。原位杂交和实时聚合酶链反应研究表明 ，所有lncRNA在SCLC / NEC中的表达都较高（p <0.01）。小型干扰RNA研究表明，MEG3和PCA3在肿瘤增殖中起作用。因此，这些lncRNAs可以作为肺NEN侵袭性的预后指标和可能的治疗靶点。