Conventional serum tumor markers (STMs) for testicular germ cell tumors (GCTs) offer limited performance 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. This study's objective was to explore miR-371a-3p's utility in detecting metastatic pure seminoma at retroperitoneal lymph node dissection (RPLND).
RNA was isolated from patient serum samples collected pre-RPLND. Fifteen patients were assigned to our 'Benign' (n = 6) or 'Seminoma' (n = 9) group based on pathological confirmation of viable seminoma. Five of the patients received chemotherapy before RPLND (PC-RPLND) and ten were chemotherapy naïve. MiR-371a-3p expression was quantified via RT-qPCR. The Cq values were statistically evaluated to obtain performance measurements.
Median relative expression of miR-371a-3p was higher in the Seminoma group than the Benign, but this difference was not statistically significant (Rq = 3705 and 241, respectively, p = 0.2844). Of the 10 chemotherapy naïve patients, 9 had viable seminoma 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 primary RPLND group presented 78% sensitivity and 100% specificity. Specificity in the PC-RPLND group was 60%. An optimal Rq threshold of 28.62 was determined by Youden's J statistic, yielding 78% sensitivity and 67% specificity. ROC analysis provided an AUC of 0.704 (95% CI: 0.43-0.98, p = 0.1949). Despite modest performance, miR-371a-3p exhibited improved sensitivity and specificity compared with conventional STMs.
MiR-371a-3p outperformed STMs in the primary RPLND settings. However, miR-371a-3p was not a robust predictor of pathology in the post-chemotherapy setting. These results suggest that pure seminoma at RPLND is a clinical context wherein the miRNA assay may require further refinement. This article is protected by copyright. All rights reserved.
Andrology. 2022 Oct 18 [Epub ahead of print]
Bendu Konneh, John T Lafin, Jeffrey Howard, Thomas Gerald, Armon Amini, Anna Savelyeva, Solomon L Woldu, Cheryl M Lewis, Liwei Jia, Vitaly Margulis, Nicholas Coleman, Cinzia Scarpini, A Lindsay Frazier, Matthew J Murray, James F Amatruda, Aditya Bagrodia
Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA., Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA., Department of Pathology, University of Cambridge, UK., Department of Pediatric Hematology and Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Cancer and Blood Disease Institute, Children's Hospital Los Angeles, Los Angeles, CA, USA.