The Novel Biomarker of Germ Cell Tumours, Micro-RNA-371a-3p, Has a Very Rapid Decay in Patients with Clinical Stage 1

Abstract

Background: Accumulating evidence suggests serum levels of microRNA (miR)-371a-3p to be a novel tumour marker of testicular germ cell tumours (GCTs). Presently, there is only limited information regarding the velocity of decline of serum levels in response to treatment.

Patients and methods: Twenty-four patients with testicular GCT (20 seminoma, 4 nonseminoma, median age 40 years) with clinical stage 1 had measurements of serum levels of miR-371a-3p preoperatively and repeatedly on the following 3 days. Three had additional tests done within 24 h after surgery. Measurement results were analysed using descriptive statistical methods.

Results: Serum levels dropped to 2.62, 1.27, and 0.47% of the preoperative level within 1, 2, and 3 days, respectively. The computed half-life amounts to 3.7-7 h. The velocity of decay is significantly associated with tumour size.

Conclusions: Serum-levels of miR-371a-3p have a short half-life of less than 12 h. The rapid decay after treatment represents a valuable feature confirming the usefulness of miR-371a-3p as a valuable serum biomarker of GCT.

Keywords: Germ cell tumour; MicroRNA-371a-3p; Nonseminoma; Seminoma; Serum biomarker.

Fig. 1.

a Box plot showing the different relative microRNA (miR)-371a-3p expressions in serum samples of patients with testicular germ cell tumours (GCTs) at consecutive time points following orchiectomy. See the Methods section for clinical details. Horizontal line within box denotes median serum relative quantity (RQ) value, upper and lower limits of boxes denote inter quartile ranges (IQRs). Whiskers show lowest and highest values within a range of 1.5 IQR. The y-axis represents a logarithmic scale. b Line graph showing the rapid decay of serum miR-371a-3p levels in 3 patients with multiple tests during the first 24 h after surgery. See the Methods section for clinical details. The y-axis represents percentages of the preoperative serum values. The horizontal dashed line depicts the 50% reduction level.

Fig. 2.

Scatter plot showing the correlation between the preoperative relative expression of miR-371a-3p and the tumour size in 24 patients with testicular germ cell tumour (GCT). The y-axis is displayed in a logarithmic scale.

Fig. 3.

Scatter plot showing the velocity of miR-371a-3p decay in relation to the tumour size. X-axis denotes tumour-size (mm); y-axis denotes the time needed to reach the cut-off level. Only those patients whose miRNA levels dropped below the cutoff value within 72 h (n = 16) are included. The figure clearly illustrates that smaller tumours arrive more rapidly at the cutoff level.