Ruiz-Plazas Xavier, Altuna-Coy Antonio, Alves-Santiago Marta, Vila-Barja José, García-Fontgivell Joan Francesc, Martínez-González Salomé, Segarra-Tomás José, Chacón Matilde R
Disease Biomarkers and Molecular Mechanisms Group, IISPV, Joan XXIII University Hospital, Universitat Rovira i Virgili, 43007 Tarragona, Spain.
Urology Unit, Joan XXIII University Hospital, 43007 Tarragona, Spain.
Cancers (Basel). 2021 Jan 11;13(2):250. doi: 10.3390/cancers13020250.
Liquid biopsy-based biomarkers, including microRNAs packaged within extracellular vesicles, are promising tools for patient management. The cytokine tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is related to PCa progression and is found in the semen of patients with PCa. TWEAK can induce the transfer of exo-oncomiRNAs from tumor cells to body fluids, and this process might have utility in non-invasive PCa prognosis. We investigated TWEAK-regulated exo-microRNAs in semen and in post-digital rectal examination urine from patients with different degrees of PCa aggressiveness. We first identified 14 exo-oncomiRNAs regulated by TWEAK in PCa cells in vitro, and subsequently validated those using liquid biopsies from 97 patients with PCa. Exo-oncomiR-221-3p, -222-3p and -31-5p were significantly higher in the semen of high-risk patients than in low-risk peers, whereas exo-oncomiR-193-3p and -423-5p were significantly lower in paired samples of post-digital rectal examination urine. A panel of semen biomarkers comprising exo-oncomiR-221-3p, -222-3p and TWEAK was designed that could correctly classify 87.5% of patients with aggressive PCa, with 85.7% specificity and 76.9% sensitivity with an area under the curve of 0.857. We additionally found that TWEAK modulated two exo-oncomiR-221-3p targets, and . Overall, we show that liquid biopsy detection of TWEAK-regulated exo-oncomiRNAs can improve PCa prognosis prediction.
基于液体活检的生物标志物，包括细胞外囊泡内包裹的微小RNA，是用于患者管理的有前景的工具。细胞因子肿瘤坏死因子样凋亡弱诱导剂（TWEAK）与前列腺癌进展相关，且在前列腺癌患者的精液中被发现。TWEAK可诱导外泌体致癌微小RNA从肿瘤细胞转移至体液，这一过程可能在前列腺癌的非侵入性预后评估中具有应用价值。我们研究了不同侵袭程度前列腺癌患者精液及直肠指检后尿液中TWEAK调控的外泌体微小RNA。我们首先在体外确定了前列腺癌细胞中14种受TWEAK调控的外泌体致癌微小RNA，随后利用97例前列腺癌患者的液体活检样本对其进行验证。高危患者精液中的外泌体致癌微小RNA-221-3p、-222-3p和-31-5p显著高于低危患者，而在直肠指检后尿液的配对样本中，外泌体致癌微小RNA-193-3p和-423-5p显著降低。设计了一组精液生物标志物，包括外泌体致癌微小RNA-221-3p、-222-3p和TWEAK，其能够正确分类87.5%的侵袭性前列腺癌患者，特异性为85.7%，敏感性为76.9%，曲线下面积为0.857。我们还发现TWEAK调节了两个外泌体致癌微小RNA-221-3p的靶标， 和 。总体而言，我们表明通过液体活检检测TWEAK调控的外泌体致癌微小RNA可改善前列腺癌预后预测。
