PD51-06: Evaluation of Mir-371a-3p Performance in Detecting Seminomatous Testicular Cancer Metastases

Bendu Konneh*, John T Lafin, Anna Savelyeva, Solomon L. Woldu, Cheryl Lewis, Vitaly Margulis, Dallas, TX, Lindsay Frazier, Boston, MA, Nicholas Coleman, Matthew Murray, Cambridge, United Kingdom, Armon Amini, Dallas, TX, James F. Amatruda, Boston, MA, Cinzia Scarpini, Cambridge, United Kingdom, Aditya Bagrodia, San Diego, CA

Introduction: Conventional serum tumor markers (STMs) for testicular germ cell tumors (GCTs) offer limited performance characteristics with particularly poor sensitivity in cases of minimal residual disease and pure seminoma. While growing evidence has indicated miR-371a-3p to be a superior biomarker, its utility in detecting pure seminoma at recurrence has not been extensively explored. The objective of this study was to explore miR-371a-3p utility in detecting metastatic pure seminoma at retroperitoneal lymph node dissection (RPLND).

Methods: Serum samples were prospectively collected from patients pre-RPLND. Fifteen patients were assigned to our ‘Control’ or ‘Seminoma’ group based on pathological confirmation of viable GCT. Within this cohort, five of the patients received chemotherapy prior to retroperitoneal lymph node dissection (RPLND) and ten were chemotherapy naïve. RNA was isolated from patient serum samples and miR-371a-3p expression was quantified via RT-qPCR. The Cq values were statistically evaluated to obtain performance measurements.

Results: Median relative expression of miR-371a-3p was higher in the Seminoma group than the Control group, but this difference was not statistically significant (Rq = 3705 and 241 respectively, p = 0.2844). Of the 10 chemotherapy naïve patients, 9 had viable GCT at RPLND and 7 had elevated miR-371a-3p expression. Among the 5 post-chemotherapy patients, 0 had viable GCT at RPLND and 2 had elevated miR-371a-3p expression. The seminoma group had 7/9 true positive results and the control group had 4/6 true negatives. The two false positives were from post-chemotherapy patients. An optimal Cq threshold of 28.62 was determined by Youden’s J statistic, yielding 78% specificity and 67% sensitivity. ROC analysis provided an AUC of 0.704 (95% CI: 0.43-0.98, p = 0.1949). Despite its modest performance in this context, miR-371a-3p exhibited improved sensitivity and specificity compared to conventional STMs.

Conclusions: Although miR-371a-3p outperformed STMs, performance characteristics were lower than previous reports that evaluated miR-371a-3p performance in pre-orchiectomy and primary RPLND settings. A possible explanation for this disparity is that miR-371a-3p’s performance is hindered in the post-chemotherapy RPLND setting. However, any strong conclusions from these results are limited by the small sample size which is partly due to the rarity of this clinical scenario. These results suggest that pure seminoma at RPLND may be a key clinical context wherein the miRNA assay may require further refinement.

Source of Funding: Cancer Prevention and Research Institute of Texas