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胰腺神经内分泌肿瘤的全基因组微小RNA分析

Global microRNA profiling of pancreatic neuroendocrine neoplasias.

作者信息

Thorns Chistoph, Schurmann Claudia, Gebauer Niklas, Wallaschofski Henri, Kümpers Christiane, Bernard Veronica, Feller Alfred C, Keck Tobias, Habermann Jens K, Begum Nehara, Lehnert Hendrik, Brabant Georg

机构信息

Institut für Pathologie, Universität zu Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany.

出版信息

Anticancer Res. 2014 May;34(5):2249-54.

Abstract

BACKGROUND

Pancreatic neuroendocrine neoplasms (pNEN) are rare tumors with a poor prognosis. Although increasing data have accumulated on the molecular pathology of pNEN, very scarce data exist on microRNAs in pNEN and no data are published on microRNAs as potential biomarkers of pNEN in serum. This study aimed to identify microRNA signatures of pNEN in tissue and serum.

MATERIALS AND METHODS

We included tissue samples from 37 patients with pNEN, 9 patients with non-neoplastic pancreatic pathology, seven samples of micro-dissected pancreatic islets and serum samples of 27 patients with pNEN, as well as of 15 healthy volunteers. MicroRNA expression profiles were established using real-time quantitative Polymerase Chain reaction (PCR) for 754 microRNAs.

RESULTS

MicroRNA signatures differed between pNEN, pancreatic islets and total pancreas, with virtually no overlap between the groups of de-regulated microRNAs. Expression of miR-642 correlated with Ki67 (MiB1) score and miR-210 correlated with metastatic disease. When comparing microRNA levels in serum from patients with pNEN and healthy volunteers, 13 microRNAs were more abundant in the serum of patients. MiR-193b was also up-regulated in pNEN tissue when compared to pancreatic islets and remained significantly increased in serum even when corrected for multiple testing.

CONCLUSION

Evaluation of microRNAs appears to be promising in the assessment of pNEN. In particular, miR-193b, which is also increased in serum, may be a potential new biomarker of pNEN.

摘要

背景

胰腺神经内分泌肿瘤(pNEN)是一种罕见的预后不良的肿瘤。尽管关于pNEN分子病理学的数据不断积累,但关于pNEN中微小RNA的资料非常稀少,且尚无关于血清中微小RNA作为pNEN潜在生物标志物的报道。本研究旨在确定pNEN组织和血清中的微小RNA特征。

材料与方法

我们纳入了37例pNEN患者的组织样本、9例非肿瘤性胰腺病变患者的组织样本、7份显微切割的胰岛样本、27例pNEN患者以及15名健康志愿者的血清样本。使用实时定量聚合酶链反应(PCR)对754种微小RNA建立微小RNA表达谱。

结果

pNEN、胰岛和整个胰腺之间的微小RNA特征不同,失调的微小RNA组之间几乎没有重叠。miR-642的表达与Ki67(MiB1)评分相关,miR-210与转移性疾病相关。比较pNEN患者和健康志愿者血清中的微小RNA水平,患者血清中有13种微小RNA更为丰富。与胰岛相比,miR-193b在pNEN组织中也上调,即使在进行多重检验校正后,其在血清中仍显著升高。

结论

微小RNA评估在pNEN评估中似乎很有前景。特别是血清中也升高的miR-193b可能是pNEN一种潜在的新生物标志物。

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