Lobo João, van Zogchel Lieke M J, Nuru Mohammed G, Gillis Ad J M, van der Schoot C Ellen, Tytgat Godelieve A M, Looijenga Leendert H J
Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, The Netherlands.
Cancer Biology and Epigenetics Group, Research Center of IPO Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), R. Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal.
Cancers (Basel). 2021 Oct 18;13(20):5228. doi: 10.3390/cancers13205228.
The classical serum tumor markers used routinely in the management of testicular germ cell tumor (TGCT) patients-alpha fetoprotein (AFP) and human chorionic gonadotropin (HCG)-show important limitations. miR-371a-3p is the most recent promising biomarker for TGCTs, but it is not sufficiently informative for detection of teratoma, which is therapeutically relevant. We aimed to test the feasibility of hypermethylated () detected in circulating cell-free DNA as a non-invasive diagnostic marker of testicular germ cell tumors, combined with miR-371a-3p. A total of 109 serum samples of patients and 29 sera of healthy young adult males were included, along with representative cell lines and tumor tissue samples. We describe a novel droplet digital polymerase chain reaction (ddPCR) method for quantitatively assessing in liquid biopsies. Both miR-371a-3p (sensitivity = 85.7%) and (sensitivity = 86.7%) outperformed the combination of AFP and HCG (sensitivity = 65.5%) for TGCT diagnosis. detected 88% of teratomas. In this representative cohort, 14 cases were negative for miR-371a-3p, all of which were detected by , resulting in a combined sensitivity of 100%. We have described a highly sensitive and specific panel of biomarkers for TGCT patients, to be validated in the context of patient follow-up and detection of minimal residual disease.
在睾丸生殖细胞肿瘤（TGCT）患者管理中常规使用的经典血清肿瘤标志物——甲胎蛋白（AFP）和人绒毛膜促性腺激素（HCG）——存在重要局限性。miR-371a-3p是TGCT最新且有前景的生物标志物，但对于检测具有治疗相关性的畸胎瘤而言，其信息不够充分。我们旨在测试循环游离DNA中检测到的高甲基化（）作为睾丸生殖细胞肿瘤的非侵入性诊断标志物并结合miR-371a-3p的可行性。共纳入了109例患者的血清样本和29例健康年轻成年男性的血清，以及代表性细胞系和肿瘤组织样本。我们描述了一种用于定量评估液体活检中（）的新型液滴数字聚合酶链反应（ddPCR）方法。对于TGCT诊断，miR-371a-3p（敏感性 = 85.7%）和（敏感性 = 86.7%）均优于AFP和HCG的联合检测（敏感性 = 65.5%）。（）检测出88%的畸胎瘤。在这个代表性队列中，14例miR-371a-3p检测为阴性的病例，所有这些病例均被（）检测到，综合敏感性达100%。我们描述了一组用于TGCT患者的高敏感性和特异性生物标志物，有待在患者随访和微小残留病检测的背景下进行验证。
