TY - JOUR
T1 - A Multi-institutional Pooled Analysis Demonstrates That Circulating miR-371a-3p Alone is Sufficient for Testicular Malignant Germ Cell Tumor Diagnosis
AU - Piao, Jin
AU - Lafin, John T.
AU - Scarpini, Cinzia G.
AU - Nuño, Michelle M.
AU - Syring, Isabella
AU - Dieckmann, Klaus Peter
AU - Belge, Gazanfer
AU - Ellinger, Jörg
AU - Amatruda, James F.
AU - Bagrodia, Aditya
AU - Coleman, Nicholas
AU - Krailo, Mark D.
AU - Frazier, A. Lindsay
AU - Murray, Matthew J.
N1 - Funding Information:
The authors acknowledge grant funding from the NIH UH2/UH3 program [reference 5UH2CA240688-02], St. Baldrick's Foundation [reference 358099] and the Isaac Newton Trust [reference 15.40f]. We are grateful for support from the Max Williamson Fund and from Christiane and Alan Hodson, in memory of their daughter Olivia. The funders were not involved in study design, data collection or interpretation, or decision to submit for publication.
Publisher Copyright:
© 2021
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
KW - Biomarker
KW - germ
KW - microRNA
KW - testis cancer
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U2 - 10.1016/j.clgc.2021.08.006
DO - 10.1016/j.clgc.2021.08.006
M3 - Article
C2 - 34629299
AN - SCOPUS:85116801277
SN - 1558-7673
VL - 19
SP - 469
EP - 479
JO - Clinical Genitourinary Cancer
JF - Clinical Genitourinary Cancer
IS - 6
ER -