Expression of the novel serum biomarker of testicular germ cell tumours miR-371a-3p in serum of pregnant women: a case-control study

妊娠妇女血清中睾丸生殖细胞肿瘤新型血清生物标志物miR-371a-3p的表达:一项病例对照研究

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Abstract

BACKGROUND: The microRNA-371a-3p (M371) is a sensitive novel serum biomarker of testicular germ cell tumours (GCTs) and a certified test is available for consistent clinical testing. In view of the well-known biological analogies of GCTs and embryogenesis, we hypothesized that the marker substance M371 is also present in serum of pregnant women. The goal of this report was to analyse maternal serum for M371. MATERIALS AND METHODS: M371 serum levels were measured in 36 third-trimester pregnant women. Control groups consisted of 12 non-pregnant young women, 12 healthy young males, and 12 patients with GCTs. M371 levels were measured by quantitative real time PCR using the certified M371 test with the standard cutoff of RQ = 5. Statistical methods involved receiver operating characteristics (ROC) analysis with Youden index analysis, and statistical comparisons of median serum levels of patients with those of controls as well as for comparisons of subgroups of patients according to age and infant sex. RESULTS: All pregnant women had measurable M371 levels, with 83.3% of the patients having elevated levels above the cutoff, while traces below cutoff were detected in the remainder. Healthy female and male controls were both below cutoff. ROC analysis revealed a 100% sensitivity and 100% specificity of the test when the cutoff of RQ = 0.4 defined by Youden index analysis was employed. The median level in pregnant women was significantly lower than that in GCT patients (10.8 [interquartile range 6.1-20.3] versus RQ = 139.5 [IQR 54.9-630.3], p < 0.001). Individual M371 levels were not associated with patient age and with infant sex. CONCLUSIONS: The evidence for elevated levels of microRNA-371a-p in maternal serum is a novel finding. This result accords with the various analogies between GCTs and embryogenesis documented previously. The finding supports the view that cells involved in human reproduction share epigenetic features with human embryonic stem cells. Further studies are required to explore if this finding could be utilized clinically.

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