Extracellular Vesicles Enriched in hsa-miR-301a-3p and hsa-miR-1293 Dynamics in Clear Cell Renal Cell Carcinoma Patients: Potential Biomarkers of Metastatic Disease
Extracellular Vesicles Enriched in hsa-miR-301a-3p and hsa-miR-1293 Dynamics in Clear Cell Renal Cell Carcinoma Patients: Potential Biomarkers of Metastatic Disease
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DOI：
10.3390/cancers12061450
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发表时间：
2020-06-01
期刊：
影响因子：
5.2
通讯作者：
Medeiros, Rui
中科院分区：
文献类型：
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作者：
Dias, Francisca;Teixeira, Ana Luisa;Medeiros, Rui
肾透明细胞癌(CcRCC)是肾癌中最具侵袭性的亚型，在接受手术治疗的患者中，高达40%的患者会复发。因此，这项研究的目的是分析细胞外小泡(EV)来源的miRNA作为ccRCC患者潜在预后生物标志物的适用性。我们分析了32例局限性肾细胞癌患者(手术前和术后)和37例转移性疾病患者血浆EVS中的9-miRNA图谱。我们观察到，术后EV来源的hsa-miR-25-3p、hsa-miR-126-5p、hsa-miR-200C-3p和hsa-miR-301a-3p水平下降，而hsa-miR-1293EV水平上升。此外，与局限性疾病患者相比，转移患者术后hsa-miR-301a-3p水平较高，hsa-miR-1293水平较低。对术后减少的四个miRNAs靶点的功能富集性分析导致了与细胞周期、增殖和代谢相关的术语的富集性，表明在肿瘤存在的情况下EV-miRNA的富集性可能代表了维持肿瘤发展的表观遗传学机制。综上所述，这些结果提示EVS含量因疾病的存在或不同而不同，EV来源的hsa-miR-301a-3p的增加和EV来源的hsa-miR-1293的减少可能是转移性肾细胞癌的潜在生物标志物。
Clear cell renal cell carcinoma (ccRCC) is the most aggressive subtype of kidney cancer and up to 40% of patients submitted to surgery with a curative intent will relapse. Thus, the aim of this study was to analyze the applicability of an Extracellular vesicle (EV) derived miRNA profile as potential prognosis biomarkers in ccRCC patients. We analyzed a nine-miRNA profile in plasma EVs from 32 ccRCC patients with localized disease (before and after surgery) and in 37 patients with metastatic disease. We observed that the levels of EV-derived hsa-miR-25-3p, hsa-miR-126-5p, hsa-miR-200c-3p, and hsa-miR-301a-3p decreased after surgery, whereas hsa-miR-1293 EV-levels increased. Furthermore, metastatic patients presented higher levels of hsa-miR-301a-3p and lower levels of hsa-miR-1293 when compared to patients with localized disease after surgery. Functional enrichment analysis of the targets of the four miRNAs that decreased after surgery resulted in an enrichment of terms related to cell cycle, proliferation, and metabolism, suggesting that EV-miRNA enrichment in the presence of the tumor could represent an epigenetic mechanism to sustain tumor development. Taken together, these results suggest that EVs content varies depending on the presence or absence of the disease and that an increase of EV-derived hsa-miR-301a-3p, and decrease of EV-derived hsa-miR-1293, may be potential biomarkers of metastatic ccRCC.