MicroRNA miR‐371a‐3p in serum of patients with germ cell tumours: evaluations for establishing a serum biomarker

Abstract

SUMMARYAs only 60% of the patients with germ cell tumour (GCT) express the classical markers, new markers as for example microRNAs (miRNAs) are required. One promising candidate is miR-371a-3p, but data are sparse to date. We measured serum levels of miR371a-3p in GCT patients, in controls, and in cases with other malignancies. We also assessed the expression in other body fluids and we looked to the decline of serum miR-371a-3p levels after treatment. miR-371a-3p levels were measured by quantitative polymerase chain reaction in serum samples of 25 GCT patients, 6 testicular intraepithelial neoplasia (TIN) patients, 20 healthy males and 24 non-testicular malignancies (NTMs). Testicular vein blood (TVB) was examined in five GCT patients and five controls. Five GCT patients had serial daily measurements after orchiectomy. Five seminal plasma samples, three urine specimens and one pleural effusion fluid were processed likewise. GCT patients had significantly higher miR-371a-3p serum levels than controls and NTMs. Serum levels of controls, TINs and NTMs were not significantly different. TVB samples of GCT patients had 65.4-fold higher serum levels than peripheral blood. Malignant pleural effusion fluid had extremely high levels of miR-371a-3p, seminal plasma had strongly elevated levels by comparison with serum levels of controls. In urine of GCT patients, no miR-371a-3p expression was detected. Daily measurements after orchiectomy in stage 1 patients revealed a decline by 95% within 24 h. Serum levels of miR-371a-3p appear to be a promising specific biomarker of GCTs as is suggested by high serum levels in GCT patients, the rapid return of elevated levels to normal range after treatment, the association of serum levels with tumour bulk, the non-expression in NTMs and the much higher levels of miR-371a-3p in TVB. This potential marker deserves further exploration in a large-scale clinical study.

The translational potential of microRNAs as biofluid markers of urological tumours

“…130 Subsequently, the expression levels of these tissue-based signatures were measured in serum. [131][132][133][134][135][136] These liquid biopsy data confirmed the potential utility of miRNA measurements for discriminating patients with seminoma or those with nonseminoma from healthy control subjects. A selected set of four miRNAs (miR-371a-3p, miR-372, miR-373 and miR-367) present in the two clusters that showed the highest discriminative power for diagnosis and follow-up of cancer, combined with reference miRNAs (miR-20a and miR-93) and spike-in controls was developed as the 'targeted serum miRNA assay' (TSmiR).…”

“…134,136 Two independent studies, confirmed these promising results for miR-371a-3p as a biomarker for testicular cancer; however these reports only included a limited number of participants. 132,133 A simplified assay for analysing miR371a-3p without endogenous controls was recommended to reduce laboratory work, analytical time and costs. 137 Results of another study confirmed the discriminative ability of serum miR-371a-3p and miR-372 concentrations and also identified numerous novel discriminative serum miRNAs (miR-511, miR-26b, miR-769, miR23a, miR-106b, miR-365, miR-598, miR-340 and let-7a), which were identified using a high-throughput profiling system, but did not validate the results.…”

Diagnostic markers for germ cell neoplasms: from placental-like alkaline phosphatase to micro-RNAs

“…pleural effusion fluid. Importantly for testicular neoplasms, seminal plasma apparently also has elevated levels of specific miRNAs compared with controls [103]. These results are very promising and it is likely that miRNA-based assays will be routinely used for diagnosis and follow-up of the patients in not so distant future.…”

MicroRNA miR-371a-3p - A Novel Serum Biomarker of Testicular Germ Cell Tumors: Evidence for Specificity from Measurements in Testicular Vein Blood and in Neoplastic Hydrocele Fluid

“…table 1; for all online suppl. material, see www.karger.com/doi/10.1159/000444303); 6 had been reported earlier [24,25]. In 33 CS1 patients, postoperative CVB samples were available, additionally.…”

“…Evidence for the specificity of serum levels of miRs-371-3 for testicular GCT is still equivocal despite the following observations: (1) high serum levels of these miRs in the majority of patients, (2) very low levels in healthy men, (3) in men suffering from non-testicular malignancies and (4) a significant decrease of levels after cure [25]. Another way of confirming the specificity of miRs-371-3 for testicular GCT would be to show particularly high levels of these miRs in body fluids being in close contact to the testicular neoplasm.…”