MicroRNAs in Penile Cancer: A Systematic Review of Diagnostic, Prognostic, and Mechanistic Evidence

Xiaohu Zhang1, Fakhri Rahman1, John D Kelly2

  • 1Division of Surgery and Interventional Sciences, University College London, London, UK.

Abstract

Insights

MicroRNAs show potential as biomarkers for penile squamous cell carcinoma (PSCC), but current evidence is insufficient for clinical use. Further validation in large cohorts is needed to establish their role in risk stratification and treatment decisions for PSCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biomarker Discovery

Background:

  • Penile squamous cell carcinoma (PSCC) is a rare cancer with limited prognostic markers.
  • MicroRNAs (miRNAs) are investigated as potential molecular markers and regulators in PSCC.

Purpose of the Study:

  • To systematically review and summarize evidence on candidate miRNAs in PSCC.
  • To assess reported diagnostic, prognostic, and mechanistic associations of miRNAs in PSCC.

Main Methods:

  • Systematic literature search of major databases (PubMed, Embase, Web of Science, Scopus) following PRISMA guidelines.
  • Inclusion of studies on miRNA expression in PSCC tissues/biofluids with clinical or mechanistic outcomes.
  • Data extraction and quality assessment using Newcastle-Ottawa Scale and GRADE framework.

Main Results:

  • Multiple dysregulated miRNAs identified with distinct profiles linked to tumor presence, metastasis, and survival.
  • Oncogenic (e.g., miR-21, miR-223) and tumor-suppressive (e.g., miR-145, miR-1) miRNAs implicated in PSCC pathways.
  • HPV-associated miRNA signatures suggest distinct molecular subtypes, but evidence is limited by small sample sizes and heterogeneity.

Conclusions:

  • Current miRNA signatures in PSCC show molecular associations but lack sufficient evidence for clinical application.
  • Large, standardized multicenter cohorts and external validation are essential for implementing miRNA-based markers in PSCC.
  • More research is needed to establish reliable miRNA biomarkers for PSCC risk stratification and clinical decision-making.

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