Department of Urology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, The Netherlands.
Pathology (LEPO), Erasmus MC Cancer Institute, University Medical Center, Rotterdam, The Netherlands.
Andrology. 2019 Jul;7(4):463-468. doi: 10.1111/andr.12595. Epub 2019 Feb 20.
The microRNA-371a-3p (miR-371a-3p) has been reported to be an informative liquid biopsy (serum and plasma) molecular biomarker for both diagnosis and follow-up of patients with a malignant (testicular) germ cell tumor ((T)GCT). It is expressed in all histological cancer elements, with the exception of mature teratoma. However, normal testis, semen, and serum of males with a disrupted testicular integrity without a TGCT may contain miR-371a-3p levels above threshold, of which the cellular origin is unknown.
Therefore, a series of relevant tissues (frozen and formalin-fixed paraffin-embedded (FFPE), when available) from the complete male urogenital tract (i.e., kidney to urethra and testis to urethra) and semen was investigated for miR-371a-3p levels using targeted quantitative RT-PCR (qRT-PCR).
In total, semen of males with normospermia (n = 11) and oligospermia (n = 3) was investigated, as well as 88 samples derived from 32 different patients. The samples represented one set of tissues related to the entire male urogenital tract (11 anatomical locations), three sets for 10 locations, and four sets for six locations.
All testis parenchyma (n = 17) cases showed low miR-371a-3p levels. Eight out of 14 (57%) semen samples showed detectable miR-371a-3p levels, irrespective of the amount of motile spermatozoa, but related to sperm concentration and matched Johnsen score (Spearman's rho correlation coefficient 0.849 and 0.871, p = 0.000, respectively). In all other tissues investigated, miR-371a-3p could not be detected.
This study demonstrates that the miR-371a-3p in healthy adult males is solely derived from the germ cell compartment.
The observation is important in the context of applying miR-371a-3p as molecular liquid biopsy biomarker for diagnosis and follow-up of patients with malignant (T)GCT. Moreover, miR-371a-3p might be an informative seminal biomarker for testicular germ cell composition.
微小 RNA-371a-3p（miR-371a-3p）已被报道为一种有信息价值的液体活检（血清和血浆）分子生物标志物，可用于诊断和随访恶性（睾丸）生殖细胞肿瘤（(T)GCT）患者。它存在于所有组织学癌症元素中，除了成熟的畸胎瘤。然而，正常的睾丸、精液和没有 TGCT 的男性睾丸完整性受损的血清可能含有高于阈值的 miR-371a-3p 水平，其细胞来源尚不清楚。
因此，使用靶向定量 RT-PCR（qRT-PCR）对完整男性尿生殖系统（即肾脏到尿道和睾丸到尿道）和精液的一系列相关组织（冷冻和福尔马林固定石蜡包埋（FFPE），如有）进行 miR-371a-3p 水平的研究。
共研究了正常精子症（n=11）和少精子症（n=3）男性的精液，以及 32 名不同患者的 88 个样本。这些样本代表了一组与整个男性尿生殖系统相关的组织（11 个解剖部位），三组组织代表 10 个部位，四组组织代表 6 个部位。
所有睾丸实质（n=17）病例均显示低 miR-371a-3p 水平。14 个精液样本中有 8 个（57%）检测到 miR-371a-3p 水平，无论有多少活动精子，但与精子浓度和匹配的 Johnsen 评分相关（Spearman 相关系数分别为 0.849 和 0.871，p=0.000）。在所有其他研究的组织中，均无法检测到 miR-371a-3p。
本研究表明，健康成年男性中的 miR-371a-3p 仅源自生殖细胞区室。
这一观察结果对于将 miR-371a-3p 作为恶性（T）GCT 患者的诊断和随访的分子液体活检生物标志物具有重要意义。此外，miR-371a-3p 可能是一种有信息价值的精液生物标志物，可用于睾丸生殖细胞组成。
