983P - Differential expression of circulating miR375 and miR371 to detect teratoma and viable germ cell malignancy

Abstract

BackgroundMicroRNAs are examined for clinical utility in active germ cell malignancies (GCM). miR-371a-3p (miR371) has a very high specificity and high sensitivity for the detection of GCM. However, in teratoma neither tissue nor serum/plasma are miR371 positive. miR375 is overexpressed in teratoma tissue, but detectability in blood and its utility is unknown. MethodsGCM patients (pts) enrolled from 10-2016 to 03-2019 in the GU biobank program at British Columbia Cancer were analyzed for plasma miR371/miR375 expression by RT-PCR and quantified by ΔΔCT method. Spike-in cel-miR-39-3p, miR-451 and miR-30b-5p were used as quality/internal controls. Sensitivity, specificity, PPV, NPV, AUC of the ROC of miR375 in detecting teratoma were analyzed. ResultsmiR375 expression was measured in 69 pts of whom 15 (22%) had pathologically confirmed residual teratoma post-chemotherapy, 4 (6%) residual post-chemotherapy mass without teratoma, 8 (11%) no evidence of residual disease post-chemotherapy, 15 (22%) metastatic seminoma and 27 (39%) CSI with no evidence of tumor. miR375 expression was significantly higher in pts with residual teratoma-post chemotherapy than in non-teratoma (p<0.0001). Concurrent miR371 and miR375 expression was evaluated in 17 pts with metastatic nonseminoma prior to and post-chemotherapy. miR371 correlated with viable GCM and disappeared after chemotherapy in all but one pt (presenting residual choriocarcinoma). Post-chemotherapy miR375 was unchanged or increased from pre-chemotherapy samples in 85% of pts with pathologically confirmed post-chemotherapy teratoma and remained low in 90% of patients with either complete response or non-teratoma after chemotherapy. Sensitivity of miR375 was 93% (95% CI: 68-99), specificity 75% (95% CI: 43-95), NPV 90% (95% CI 95%: 57-98), PPV 82% (CI 95%: 63-93) and the AUC of miR375 in the post-chemotherapy setting was 0.93 (95% CI: 0.83-1.0; p<0.0001). ConclusionsmiR375 is overexpressed and detectable in the plasma of pts with teratoma while its expression is significantly lower in nonseminoma pts without teratoma or in seminoma. The evaluation of miR371/miR375 may be clinically useful to guide therapeutic decisions (surgery or chemotherapy). Larger studies are warranted. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.