Di Fazio Pietro, Maass Moritz, Roth Silvia, Meyer Christian, Grups Joana, Rexin Peter, Bartsch Detlef K, Kirschbaum Andreas
1 Department of Visceral, Thoracic and Vascular Surgery, Philipps University of Marburg, Marburg, Germany.
2 Institute for Pathology, Philipps University of Marburg, Marburg, Germany.
Tumour Biol. 2017 Oct;39(10):1010428317728417. doi: 10.1177/1010428317728417.
Typical and atypical carcinoid tumors belong to the neuroendocrine lung tumors. They have low recurrence and proliferation rate, lymph node, and distant metastases. Nevertheless, these tumors have shown a more aggressive behavior. In the last years, microRNAs were screened as new tumor markers for their potential diagnostic and therapeutic relevance. The expression of hsa-let-7b-5p, hsa-let-7f-5p, hsa-miR-222-3p, and their targets HMGA2 (high-mobility group A2) and CDKN1B (cyclin-dependent kynase inhibitor 1B, p27) was evaluated in this rare small group of patients. We analyzed the clinical data of all typical and atypical carcinoid tumors of patients who underwent surgical operation at Marburg University Hospital (n = 18) from 2000. Quantitative reverse transcription polymerase chain reaction was performed in formalin-fixed paraffin-embedded tumor tissue versus four tumor-free lung tissue samples. HMGA2 was stable or downregulated; only one patient showed a significant overexpression. CDKN1B showed a significant overexpression or a stable level; it was downregulated in two samples only. Hsa-miR-222-3p resulted almost stable or overexpressed except for two samples (significantly downregulated). Hsa-let-7f-5p was stable or overexpressed in the majority of analyzed samples, whereas hsa-let-7b-5p was significantly downregulated. HMGA2 and CDKN1B are differently expressed between atypical and typical carcinoid tumors, thus representing valid biomarkers for the classification of the two tumor groups. Hsa-let-7f-5p and HMGA2 are inversely correlated. Hsa-miR-222-3p does not correlate with its predicted target CDKN1B.
典型类癌和非典型类癌肿瘤属于神经内分泌性肺肿瘤。它们的复发率和增殖率较低,较少发生淋巴结转移和远处转移。然而,这些肿瘤已表现出更具侵袭性的行为。近年来,微小RNA因其潜在的诊断和治疗相关性而被筛选为新的肿瘤标志物。在这一罕见的小患者群体中评估了hsa-let-7b-5p、hsa-let-7f-5p、hsa-miR-222-3p及其靶标HMGA2(高迁移率族蛋白A2)和CDKN1B(细胞周期蛋白依赖性激酶抑制剂1B,p27)的表达。我们分析了2000年以来在马尔堡大学医院接受手术的所有典型和非典型类癌肿瘤患者的临床资料(n = 18)。在福尔马林固定石蜡包埋的肿瘤组织与四个无肿瘤的肺组织样本中进行了定量逆转录聚合酶链反应。HMGA2表达稳定或下调;仅1例患者出现显著过表达。CDKN1B表现为显著过表达或水平稳定;仅在两个样本中下调。hsa-miR-222-3p除两个样本(显著下调)外几乎表达稳定或过表达。hsa-let-7f-5p在大多数分析样本中表达稳定或过表达,而hsa-let-7b-5p显著下调。HMGA2和CDKN1B在非典型类癌和典型类癌肿瘤之间表达不同,因此是这两种肿瘤分类的有效生物标志物。hsa-let-7f-5p与HMGA2呈负相关。hsa-miR-222-3p与其预测靶标CDKN1B不相关。