Penile squamous cell carcinoma (PSCC) is a rare malignancy associated with substantial morbidity and limited prognostic biomarkers. MicroRNAs have been reported as candidate molecular markers and putative regulators of tumor biology in individual PSCC studies, but their clinical relevance remains uncertain.
This systematic review aimed to map and summarize current evidence on candidate miRNAs in PSCC, with emphasis on reported diagnostic, prognostic, and mechanistic associations.
A systematic literature search of PubMed, Embase, Web of Science, and Scopus was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies investigating miRNA expression in PSCC tissues or biofluids and reporting clinical or mechanistic outcomes were included. Data extraction and quality assessment were performed independently by two reviewers using the Newcastle-Ottawa Scale and Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework.
Multiple dysregulated miRNAs were identified, with distinct profiles associated with tumor presence, lymph node metastasis, and survival outcomes. Oncogenic miRNAs such as miR-21 and miR-223 were reported in studies implicating PTEN/PI3K/AKT and invasion-related pathways, while tumor-suppressive miRNAs including miR-145 and miR-1 were reported as downregulated in selected studies of metastatic or adverse clinicopathological disease. HPV-associated miRNA signatures demonstrated divergent regulatory patterns, reflecting distinct molecular subtypes of PSCC. However, evidence was limited by small sample sizes, methodological heterogeneity, and lack of external validation.
Reported miRNA signatures represent molecular associations in PSCC, but current evidence is insufficient to support risk stratification or clinical decision-making. Standardized, large multicenter cohorts and independent external validation are required before any miRNA-based marker can be considered for clinical implementation in PSCC.
European urology focus. 2026 Jul 15 [Epub ahead of print]
Xiaohu Zhang, Fakhri Rahman, John D Kelly, Hussain M Alnajjar, Asif Muneer, Karl H Pang
Division of Surgery and Interventional Sciences, University College London, London, UK., Division of Surgery and Interventional Sciences, University College London, London, UK; Department of Urology, University College London Hospitals NHS Foundation Trust, London, UK., Division of Surgery and Interventional Sciences, University College London, London, UK; Department of Urology, University College London Hospitals NHS Foundation Trust, London, UK; National Institute for Health and Research, University College London Hospitals, Biomedical Research Centre, London, UK. Electronic address: ., Division of Surgery and Interventional Sciences, University College London, London, UK; Department of Urology, Chelsea and Westminster Hospital NHS Foundation Trust, London, UK. Electronic address: .