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.
Keywords
Abbreviations:
AFP (alpha-fetoprotein), AUC (area-under-the-curve), CNS (central nervous system), Cq (cycle threshold), HCG (human-chorionic-gonadotrophin), LDH (lactate dehydrogenase), MGCT (malignant germ-cell-tumor), miRNA (microRNA), NPV (negative-predictive-value), PCR (polymerase chain reaction), PPV (positive-predictive-value), UTSW (University of Texas Southwestern Medical Center, Dallas, TX, US), Youden Index (YI)To read this article in full you will need to make a payment
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Article Info
Publication History
Published online: September 14, 2021
Accepted:
August 28,
2021
Received in revised form:
August 26,
2021
Received:
March 25,
2021
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2021 Elsevier Inc. All rights reserved.
