Year: 2023
Type: article
Study design: Observational Study
Abstract: Circulating miR-371a-3p has excellent performance in the detection of viable (non-teratoma) germ cell tumor (GCT) pre-orchiectomy; however, its ability to detect occult disease is understudied. To refine the serum miR-371a-3p assay in the minimal residual disease setting we compared performance of raw (Cq) and normalized (∆Cq, RQ) values from prior assays, and validated interlaboratory concordance by aliquot swapping. Revised assay performance was determined in a cohort of 32 patients suspected of occult retroperitoneal disease. Assay superiority was determined by comparing resulting receiver-operator characteristic (ROC) curves using the Delong method. Pairwise t-tests were used to test for interlaboratory concordance. Performance was comparable when thresholding based on raw Cq vs. normalized values. Interlaboratory concordance of miR-371a-3p was high, but reference genes miR-30b-5p and cel-miR-39-3p were discordant. Introduction of an indeterminate range of Cq 28-35 with a repeat run for any indeterminate improved assay accuracy from 0.84 to 0.92 in a group of patients suspected of occult GCT. We recommend that serum miR-371a-3p test protocols are updated to (a) utilize threshold-based approaches using raw Cq values, (b) continue to include an endogenous (e.g., miR-30b-5p) and exogenous non-human spike-in (e.g., cel-miR-39-3p) microRNA for quality control, and (c) to re-run any sample with an indeterminate result.
Source: Scientific Reports
Authors: John T. Lafin, Cinzia G. Scarpini, Armon Amini, Bendu Konneh, Jeffrey M. Howard, Thomas Gerald, Michelle Nuno, Jin Piao, Anna Savelyeva, Zhaohui Wang, Jeffrey Gagan, Liwei Jia, Cheryl M. Lewis, Sarah Murray, Yun C. Sawa, Vitaly Margulis, Solomon L. Woldu, Douglas W. Strand, Nicholas Coleman, James F. Amatruda, A. Lindsay Frazier, Matthew J. Murray, Aditya Bagrodia
Institutions: The University of Texas Southwestern Medical Center, University of Cambridge, University of Southern California, University of California San Diego, Cambridge University Hospitals NHS Foundation Trust, Children's Hospital Los Angeles, Dana-Farber/Boston Children's Cancer and Blood Disorders Center
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,390
Awards: G1424491230, Assay Validation of a Circulating miRNA Test for Diagnosis and Monitoring of Malignant Germ Cell Tumors, G428461830, G4834239603, Assay Validation of a Circulating miRNA Test for Diagnosis and Monitoring of Malignant Germ Cell Tumors, Targeting the HNF4A and WNT/Beta-catenin pathways in childhood malignant yolk sac tumors., UT Southwestern Medical Center Simmons Comprehensive Cancer Center
OpenAlex ID: W4382631728