Goričar Katja, Holcar Marija, Mavec Nina, Kovač Viljem, Lenassi Metka, Dolžan Vita
Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia.
Institute of Oncology Ljubljana, Zaloška 2, 1000 Ljubljana, Slovenia.
J Pers Med. 2021 Oct 9;11(10):1014. doi: 10.3390/jpm11101014.
Malignant mesothelioma (MM) is characterized by poor prognosis and short survival. Extracellular vesicles (EVs) are membrane-bound particles released from cells into various body fluids, and their molecular composition reflects the characteristics of the origin cell. Blood EVs or their miRNA cargo might serve as new minimally invasive biomarkers that would enable earlier detection of MM or treatment outcome prediction. Our aim was to evaluate miRNAs enriched in serum EVs as potential prognostic biomarkers in MM patients in a pilot longitudinal study. EVs were isolated from serum samples obtained before and after treatment using ultracentrifugation on 20% sucrose cushion. Serum EV-enriched miR-103-3p, miR-126-3p and miR-625-3p were quantified using qPCR. After treatment, expression of miR-625-3p and miR-126-3p significantly increased in MM patients with poor treatment outcome ( = 0.012 and = 0.036, respectively). A relative increase in miR-625-3p expression after treatment for more than 3.2% was associated with shorter progression-free survival (7.5 vs. 19.4 months, HR = 3.92, 95% CI = 1.20-12.80, = 0.024) and overall survival (12.5 vs. 49.1 months, HR = 5.45, 95% CI = 1.06-28.11, = 0.043) of MM patients. Bioinformatic analysis showed enrichment of 33 miR-625-3p targets in eight biological pathways. Serum EV-enriched miR-625-3p could therefore serve as a prognostic biomarker in MM and could contribute to a more personalized treatment.
恶性间皮瘤（MM）的特点是预后差、生存期短。细胞外囊泡（EVs）是从细胞释放到各种体液中的膜结合颗粒，其分子组成反映了起源细胞的特征。血液中的EVs或其携带的miRNA可能作为新的微创生物标志物，实现MM的早期检测或治疗结果预测。我们的目的是在一项初步纵向研究中，评估血清EVs中富集的miRNA作为MM患者潜在的预后生物标志物。使用20%蔗糖垫层超速离心法从治疗前后采集的血清样本中分离出EVs。使用qPCR对血清中富含EVs的miR-103-3p、miR-126-3p和miR-625-3p进行定量。治疗后，治疗效果差的MM患者中miR-625-3p和miR-126-3p的表达显著增加（分别为P = 0.012和P = 0.036）。治疗后miR-625-3p表达相对增加超过3.2%与MM患者无进展生存期缩短（7.5个月对19.4个月，HR = 3.92，95%CI = 1.20 - 12.80，P = 0.024）和总生存期缩短（12.5个月对49.1个月，HR = 5.45，95%CI = 1.06 - 28.11，P = 0.043）相关。生物信息学分析显示，33个miR-625-3p靶标在8条生物学途径中富集。因此，血清中富含EVs的miR-625-3p可作为MM的预后生物标志物，并有助于实现更个性化的治疗。
