A Multi-institutional Pooled Analysis Demonstrates That Circulating miR-371a-3p Alone is Sufficient for Testicular Malignant Germ Cell Tumor Diagnosis

Jin Piao, John T. Lafin, Cinzia G. Scarpini, Michelle M. Nuño, Isabella Syring, Klaus Peter Dieckmann, Gazanfer Belge, Jörg Ellinger, James F Amatruda, Aditya Bagrodia, Nicholas Coleman, Mark D. Krailo, A. Lindsay Frazier, Matthew J. Murray

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Background: Circulating microRNAs have clear potential for improving malignant germ-cell-tumor (MGCT) diagnosis. Here, we address the central issue of whether measurement of a single microRNA is sufficient for detecting testicular MGCTs, or whether there is added benefit in quantifying other members of the 4-microRNA panel previously identified (miR-371a-3p/miR-372-3p/miR-373-3p and miR-367-3p). Patients and Methods: We performed a pooled analysis of available published raw data where all 4 panel miRNAs had been assessed using pre-amplification PCR technology (4 studies; total 329 patients). Two studies using identical methodology (and identical normalization using endogenous miR-30b-5p) were used in the discovery phase (n = 51 patients: 17 MGCT, 34 controls). The 2 other studies (n = 278 patients: 140 MGCT, 138 controls), which assessed the same test panel but with different normalization approaches (endogenous miR-93-5p, exogenous cel-miR-39-3p), were used for the validation phase. We derived sensitivity, specificity, positive- and negative-predictive-values (PPV/NPV) for the detection thresholds that maximised the Youden Index (YI). Results: In the discovery-phase, the YI was 0.97 for miR-371a-3p (sensitivity = 1, specificity = 0.97), 0.71 (miR-367-3p), 0.68 (miR-372-3p), and 0.50 (miR-373-3p). These findings were confirmed in the validation-phase, with YI of 0.75 for miR-371a-3p (sensitivity = 0.90, specificity 0.85), 0.55 (miR-367-3p), 0.47 (miR-372-3p), and 0.51 (miR-373-3p). Importantly, no combination of markers added additional diagnostic benefit to miR-371a-3p alone, in either the discovery or the validation phase. Conclusion: Quantifying circulating miR-371a-3p alone is sufficient for testicular MGCT diagnosis. PCR measurement of this single miRNA marker will be more cost-effective and easier to interpret, facilitating future incorporation into routine clinical practice.

Original languageEnglish (US)
JournalClinical Genitourinary Cancer
DOIs
StateAccepted/In press - 2021

Keywords

  • Biomarker
  • germ
  • microRNA
  • testis cancer

ASJC Scopus subject areas

  • Oncology
  • Urology

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