MicroRNA (miRNA) dysregulation is implicated in testicular germ cell tumor (TGCT) pathogenesis. Here, we characterized miRNA expression profiles across TGCT histologic subtypes using miRNA-sequencing on 43 formalin-fixed paraffin-embedded (FFPE) tissue samples (31 primary, 12 metastases) from 29 patients to identify diagnostic markers and their regulatory functions.
From 20 seminomas (SEM), 14 non-seminomatous germ cell tumors (N-SEM), and 9 teratomas, we profiled a total of 2606 miRNAs. Compared to teratomas, 154 miRNAs (targeting 657 genes) were enriched in SEM, and 141 miRNAs (targeting 358 genes) in N-SEM. miR-200-3p, targeting the DNA methyltransferase DNMT3B, was enriched in N-SEM versus SEM. Our findings showed high concordance with The Cancer Genome Atlas (TCGA)-TGCT data (Pearson R > 0.66, p < 1e-10). miRNA expression was largely similar between primary and metastatic tissues and between chemotherapy-treated and untreated teratomas, reflecting teratoma chemo-resistance. Using novel candidates, miRNA-based logistic regression classifiers distinguished viable GCT (SEM/N-SEM) from teratoma (Area Under the Curve [AUC] > 0.96) and SEM from N-SEM (AUC = 0.81), outperforming well-known miRNA markers. Target gene analysis implicated FOXO and RUNX1 regulation, somatotroph signaling, and height-related pathways. Overall, our comprehensive tissue-level miRNA profiling in TGCTs identified potential diagnostic biomarkers for histologic subtypes, offering insights into miRNA-mediated transcriptional dysregulation.
Scientific reports. 2025 Oct 21*** epublish ***
Taibo Li, Anirudh Yerrapragada, Stephan Brönimann, Carlos Rivera Lopez, Joseph Cheaib, Yasser Ged, Ezra Baraban, Shawn E Lupold, Nirmish Singla
Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Park 213, Baltimore, MD, 21287, USA., Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Park 213, Baltimore, MD, 21287, USA. .
PubMed http://www.ncbi.nlm.nih.gov/pubmed/41120510