Defining the prognostic role of MicroRNAs in cutaneous melanoma
Open accessAbstract
Breslow thickness (BT) is the most important histopathologic factor for primary melanoma staging. BT determines the margins for wide local excision whether sentinel lymph node biopsy should be performed and subsequent melanoma staging, and patient management. The correct determination of a 0.8-mm cutoff in melanoma is important for pathologists because discrepancies leading to a change in stage can have significant clinical implications, including incorrect and/or inappropriate prognostic information, investigation, management, and follow-up. Difficulties in BT determination are mostly represented by the presence of regression or melanoma associated with a pre-existing nevus. This study aimed at investigating a molecular parameter, namely microRNA (miRNA) expression, in reference to BT assessment. Melanoma cell proliferation is influenced by miRNA dysregulation. Indeed, some miRNAs sustain and induce proliferative signals or repress growth-suppressive pathways, thereby promoting melanoma carcinogenesis. To identify the miRNAs correlating with BT, we analyzed our global miRNA expression data of 20 thin melanomas and identified two potential candidates, miR-21-5p and miR-146a-5p. We assessed the expression of these two specific miRNAs in 90 archive formalin-fixed and paraffin-embedded samples of superficially spreading melanomas (SSMs) and 25 nodular melanomas from two independent cohorts and correlated the individual and combined miRNA expression with BT and other tumor characteristics. The individually normalized expression of miR-21-5p and miR-146a-5p showed a highly significant and linear correlation with BT in SSM, and their combined expression value was more strongly correlated (Pearson's r = 0.799, 95% CI = 0.71-0.86) than their individual expressions. This correlation was not significant in nodular melanoma. In SSM, we observed that the combined miRNA expression above or below 1.5 was significantly associated with overall survival and successfully identified all patients with relapsing SSM. We concluded that the combined assessment of miR-21-5p and miR-146a-5p expression in superficially spreading melanoma, in association with BT measurement, could aid pathologists in SSM staging.
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miR-21-5p and miR-146a-5p exhibit a substantial correlation with Breslow thickness in superficially spreading melanoma and may enhance standard histopathologic evaluation.
“Recent studies have highlighted the predictive significance of microRNA expression—specifically miR-21-5p and miR-146a-5p—as molecular markers that exhibit a substantial correlation with Breslow thickness in superficially spreading melanoma and may enhance standard histopathologic evaluation (8).”
From Revolutionizing dermatopathology using AI in skin diagnostics: scoping review (2026) · cites this paper as [8]
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Lamberti, J., Memoli, D., Montico, B., Silvestro, F., Guerrieri, R., Colizzi, F., Weisz, A., Salvati, A., Fratta, E., & Nassa, G. (2025) · Scientific Data · doi:10.1038/s41597-025-05807-x · Cited by 1 · see citing works
“As a result, an increasing amount of studies have investigated the predictive and prognostic potential of specific miRNA signatures in CM 28,29 .”
Paysano, M. L. B. D. A., Kreuz, M., Rebelo, T. G., Talah, B. A. D., Lôbo, A. D. O. M., da Silva, E. R., & de Moraes, F. C. A. (2026) · Melanoma Research · doi:10.1097/cmr.0000000000001090
Towards Accurate Breslow Measurements: Mitigating Issues in Histopathological Imaging
Curti, N., Dall’Olio, L., Veronesi, G., Querzoli, G., Venturi, F., Sisi, A., Peluso, S., Castellani, G., & Dika, E. (2026) · Entropy · doi:10.3390/e28060643
Circulating tumor cells as biomarkers in melanoma: techniques, challenges, and clinical applications
Broseghini, E., Durante, G., Soru, A., Bianchi, F., Comito, F., Dika, E., Ferracin, M., & Gallerani, G. (2026) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2026.1857720
“In early-stage melanoma (stages I–II), key prognostic features include Breslow thickness, ulceration, mitotic rate, and tumor-infiltrating lymphocytes (TILs) (Dika et al., 2020; Scolyer et al., 2020).”
Thin Nevus-Associated Melanoma: Beyond MIA Score Risk Stratification
Venturi, F., Orlando, M. L., Corti, B., Marchese, P. V., Comito, F., Melotti, B., Magnaterra, E., Scotti, B., Alessandrini, A. M., Veneziano, L., et al. (2026) · Cancers · doi:10.3390/cancers18152456
“…in thin nevus-associated melanoma, exploration of quantitative or AI-assisted TIL scoring methods to enhance prognostic accuracy, and investigation of emerging biomarkers such as gene expression profiling or circulating tumor DNA to complement conventional clinicopathologic assessment [53–59].”
Venturi, F., & Dika, E. (2026) · Onco · doi:10.3390/onco6030039
Venturi, F., Baraldi, C., Corti, B., Melotti, B., Magnaterra, E., Scotti, B., & Dika, E. (2026) · Cancers · doi:10.3390/cancers18172858
Reynolds, A. Z., Corcoran, D. L., Luo, L., Busam, K. J., Lezcano, C. M., Amos, C. I., Argibay, D., Shen, R., Begg, C. B., Thomas, N. E., et al. (2026) · medRxiv · doi:10.64898/2026.09.04.26362289
Skin-Derived Non-Coding RNAs as Potential Biomarkers and Therapeutic Targets
Zen, J. L., Le, Q. M. N., Li, S., & Hanna, G. B. (2026) · Non-Coding RNA · doi:10.3390/ncrna12050038
“Evaluating primary melanoma, Dika et al. [70] demonstrated that combined tissue expression of miR-21-5p and miR-146a-5p correlated with Breslow thickness and predicted overall survival in patients with superficially spreading melanoma.”
- Authors
- Dika, E., Riefolo, M., Porcellini, E., Broseghini, E., Ribero, S., Senetta, R., Osella-Abate, S., Scarfì, F., Lambertini, M., Veronesi, G., Patrizi, A., Fanti, P. A., & Ferracin, M.
- Affiliations
- IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola (IT)
- University of Bologna (IT)
- University of Turin (IT)
- Corresponding author
- Dika, Emi
- ORCID
- Venue
- Journal of Investigative Dermatology
- Publisher
- Elsevier BV
- Published
- 2020-11
- Volume
- 140
- Issue
- 11
- Pages
- 2260-2267
- ISSN
- 0022-202X (ISSN-L)
- OpenAlex
- W3015584316
- Cited by
- 39
- References
- 46
- Citations by year
- 2026: 12 · 2025: 8 · 2024: 4 · 2023: 4 · 2022: 5 · 2021: 5 · 2020: 1
- FWCI
- 1.28
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Investigative Dermatology (publishedVersion)
- PubMed (publishedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
- Funders
- Associazione Italiana per la Ricerca sul Cancro
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Health Sciences › Medicine › Oncology › Cutaneous Melanoma Detection and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Keywords
- cutaneous melanoma, Breslow thickness, microRNA expression, miR-21-5p, miR-146a, nodular melanoma, tumor staging, prognostic factors, overall survival, melanoma regression, sentinel lymph node biopsy
- MeSH terms
- Adult, Aged, Aged, 80 and over, Female, Humans, Male, Melanoma, Middle Aged, Prognosis, Skin Neoplasms, MicroRNAs
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