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Serum microRNA-371a-3p levels to predict viable germ cell tumor in chemotherapy-naïve patients undergoing retroperitoneal lymph node dissection.

Abstract

417
Background: Serum microRNAs are candidate biomarkers for diagnosing and monitoring germ cell tumors (GCTs). The ability of miRNA to inform treatment in low-stage chemotherapy-naïve patients is unexplored. We sought to evaluate the performance characteristics of serum miRNA levels to predict viable GCT in chemotherapy-naïve patients undergoing primary retroperitoneal lymph node dissection (RPLND). Methods: We prospectively collected presurgical serum samples and clinicopathologic characteristics from consecutive chemotherapy-naïve GCT patients undergoing primary RPLND from 2016-2019. Serum miRNAs (-367-3p/-371a-3p/-372-3p/-373-3p/-375) were isolated and quantified. RPLND histopathology was categorized as benign, viable GCT, or teratoma; miRNA levels were compared among groups. Performance characteristics, including receiver operating characteristic (ROC) curves, assessed the discriminative ability of each miRNA signature to predict viable GCT. Results: 24 patients with stage I-II GCT underwent RPLND, revealing viable GCT in 11 (46%), teratoma in 3 (13%), and benign pathology in 10 (42%) patients. miR-371a-3p was the most discriminatory serum miRNA for viable GCT, exhibiting ~13,000-fold increase in expression over teratoma or benign pathology. On ROC analysis, miR-371a-3p had AUC = 0.965, with sensitivity and specificity of 100% and 92%, respectively. The AUC for other serum miRNAs in predicting viable GCT were 0.874 (miR-367-3p), 0.846 (miR-372-3p), and 0.720 (miR-373-3p). These serum miRNAs were not predictive of pure teratoma. Potential limitations include small cohort size and no post-RPLND sera for comparison. Conclusions: Serum miRNAs, particularly miR-371a-3p, can accurately differentiate small-volume viable GCT from benign processes or teratoma in patients with negative serum tumor markers undergoing primary RPLND. If validated, these data suggest a basis to implement precision medicine strategies in treating patients with early-stage GCT.

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Journal of Clinical Oncology
Pages: 417

History

Published online: February 19, 2020
Published in print: February 20, 2020

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Nirmish Singla
University of Texas Southwestern Medical Center, Dallas, TX;
John T. Lafin
University of Texas Southwestern Medical Center, Dallas, TX;
Solomon L. Woldu
University of Texas Southwestern Medical Center, Dallas, TX;
Yair Lotan
The University of Texas Southwestern Medical Center, Dallas, TX;
Cheryl Lewis
University of Texas Southwestern Medical Center, Dallas, TX;
Kuntal Majmudar
University of Texas Southwestern Medical Center, Dallas, TX;
Anna Savalyeva
University of Texas Southwestern Medical Center, Dallas, TX;
Alexander P. Kenigsberg
University of Texas Southwestern Medical Center, Dallas, TX;
Payal Kapur
University of Texas Southwestern Medical Center, Dallas, TX;
Vitaly Margulis
University of Texas Southwestern Medical Center, Dallas, TX;
Douglas Strand
University of Texas Southwestern Medical Center, Dallas, TX;
Matthew Murray
Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom;
James F. Amatruda
Massachusetts General Hospital, Boston, MA;
Aditya Bagrodia
University of Texas Southwestern Medical Center, Dallas, TX;
University of Texas Southwestern Medical Center, Dallas, TX; The University of Texas Southwestern Medical Center, Dallas, TX; Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom; Massachusetts General Hospital, Boston, MA

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Funding Information

Cprit rp170152.
U.S. National Institutes of Health.
Dedman family scholarship in Clinical care.

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Nirmish Singla, John T. Lafin, Solomon L. Woldu, Yair Lotan, Cheryl Lewis, Kuntal Majmudar, Anna Savalyeva, Alexander P. Kenigsberg, Payal Kapur, Vitaly Margulis, Douglas Strand, Matthew Murray, James F. Amatruda, Aditya Bagrodia
Journal of Clinical Oncology 2020 38:6_suppl, 417-417

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