Risk Factors for Melanoma Survival: DGCR8 as a Predictive Factor for Mortality in Young Patients

Authors

  • Fabiola Schafer Department of Medical Specialties, School of Medicine, Universidad de La Frontera, Temuco, Chile https://orcid.org/0000-0003-4381-1754
  • Enrique Bellolio Department of Pathological Anatomy, School of Medicine, Universidad de La Frontera, Temuco, Chile
  • Tatiana Sepúlveda Department of Pathological Anatomy, School of Medicine, Universidad de La Frontera, Temuco, Chile
  • Mirta Espinoza Department of Pathological Anatomy, School of Medicine, Universidad de La Frontera, Temuco, Chile; Doctoral Program in Medical Science, Universidad de La Frontera, Temuco, Chile
  • Juan-Jose Orellana Department of Public Health and Capacitación, Investigación y Gestión para la Salud Basada en Evidencias (CIGES), School of Medicine, Universidad de La Frontera, Temuco, Chile
  • Miguel Angel Villaseca Department of Pathological Anatomy, School of Medicine, Universidad de La Frontera, Temuco, Chile
  • Rodrigo Miranda School of Medicine, Faculty of Health Sciences and Center for Research, Innovation and Creation (CIIC), Universidad Católica de Temuco, Chile

DOI:

https://doi.org/10.2340/actadv.v106.44513

Keywords:

DGCR8, melanoma, survival, age, mortality

Abstract

MicroRNA-processing enzymes – Dicer and DGCR8 – have been found to be dysregulated in melanoma. This study investigated whether these microRNA-processing enzymes could be used as risk factors for mortality. A retrospective cohort including medical history and samples of 74 patients was reviewed. Clinical and pathological variables were compared with mortality. Percentage of immunoreactive tumour cells (%IRC) for each enzyme was evaluated using immunohistochemistry. A dichotomous breakdown of DGCR8 and Dicer expression (negative or positive test) was performed using a cut-off of 80% IRC. The 5-year survival rate of stage 0–I–II was 89.5% and stage III–IV was 18.5%. In the bivariate analysis, variables associated with lower survival were: aged over 42 years, histologic subtypes, Breslow thickness ≥ 0.8mm, ulceration, vascular invasion, metastatic melanoma, positive sentinel node, more than 1 positive node, LDH > 200 IU/L, distant metastasis, and stage III–IV. In the multivariate Cox model, the analysis for stage III–IV showed a significantly lower survival curve in patients with a positive DGCR8 test and aged ≤ 42 years (p = 0.0152, Wald test). The Cox proportional hazards model showed that a positive DGCR8 test was a predictive factor for mortality in patients aged ≤ 42 years (HR = 14.3, 95%CI 1.5–140, p = 0.024). This study highlights a potential biomarker for melanoma survival and its utility in stratifying high-risk patients.

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References

Gershenwald JE, Scolyer RA, Hess KR, Sondak VK, Long GV, Ross MI, et al. Melanoma staging: evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin 2017; 67: 472–492. DOI: https://doi.org/10.3322/caac.21409

Michielin O, Atkins MB, Koon HB, Dummer R, Ascierto PA. Evolving impact of long-term survival results on metastatic melanoma treatment. J Immunother Cancer 2020; 8: e000948. DOI: https://doi.org/10.1136/jitc-2020-000948

Robert C, Long GV, Brady B, Dutriaux C, di Giacomo AM, Mortier L, et al. Five-year outcomes with nivolumab in patients with wild-type BRAF advanced melanoma. J Clin Oncol 2020; 38: 3937–3946. DOI: https://doi.org/10.1200/JCO.20.00995

Reed K, Brewer J, Lohse, C, Bringe K, Pruitt C, Gibsona L. Increasing incidence of melanoma among young adults: an epidemiological study in Olmsted County, Minnesota. Mayo Clin Proc 2012; 87: 328–334. DOI: https://doi.org/10.1016/j.mayocp.2012.01.010

Weir H, Marrett L, Cokkinides V, Barnholtz-Sloan J, Patel P, Tai E, et al. Melanoma in adolescents and young adults (ages 15–39 years): United States, 1999–2006. J Am Acad Dermatol 2011; 65: S38–49. DOI: https://doi.org/10.1016/j.jaad.2011.04.038

Wojcik K, Hawkins M, Anderson-Mellies A, Hall E, Wysong A, Milam J, et al. Melanoma survival by age group: population-based disparities for adolescent and young adult patients by stage, tumor thickness, and insurance type. J Am Acad Dermatol 2023; 88: 831–840. DOI: https://doi.org/10.1016/j.jaad.2022.10.063

Howman-Giles R, Shaw HM, Scolyer RA, Murali R, Wilmott J, McCarthy S, et al. Sentinel lymph node biopsy in pediatric and adolescent cutaneous melanoma patients. Ann Surg Oncol 2010; 17: 138–143. DOI: https://doi.org/10.1245/s10434-009-0657-4

Mu E, Lange J, Strouse J. Comparison of the use and results of sentinel lymph node biopsy in children and young adults with melanoma. Cancer 2012; 118: 2700–2707. DOI: https://doi.org/10.1002/cncr.26578

Sand M, Gambichler T, Sand D, Altmeyer P, Stuecker M, Bechara FG. Immunohistochemical expression patterns of the microRNA-processing enzyme Dicer in cutaneous malignant melanomas, benign melanocytic nevi and dysplastic melanocytic nevi. Eur J Dermatol 2011; 21: 18–21. DOI: https://doi.org/10.1684/ejd.2011.1210

Schafer F, Bellolio E, Sepulveda T, Espinoza Mirta, Orellana JJ, Bellolio I, et al. Characteristics of the MicroRNA-processing enzymes in melanocytic skin lesions: Dicer and DGCR8 are potential biomarkers for primary cutaneous melanomas. Exp Dermatol 2025; 34: e70110. DOI: https://doi.org/10.1111/exd.70110

Ma Z, Swede H, Cassarino D, Fleming E, Fire A, Dadras S. Up-regulated Dicer expression in patients with cutaneous melanoma. PLoS One 2011; 6: e20494. DOI: https://doi.org/10.1371/journal.pone.0020494

Ruan K, Fang X, Ouyang G. MicroRNAs: novel regulators in the hallmarks of human cancer. Cancer Letters 2009; 285: 116–126. DOI: https://doi.org/10.1016/j.canlet.2009.04.031

Kim B, Lee J, Park J, Kwon T, Baek S, Hwang I, et al. An essential microRNA maturing microprocessor complex component DGCR8 is up-regulated in colorectal carcinomas. Clin Exp Med 2014; 14: 331–336. DOI: https://doi.org/10.1007/s10238-013-0243-8

Gomez-Cabello D, Adrados I, Gamarra D, Kobayashi H, Takatsu H, Takatsu K, et al. DGCR8-mediated disruption of miRNA biogenesis induces cellular senescence in primary fibroblasts. Aging Cell 2013; 12: 923–931. DOI: https://doi.org/10.1111/acel.12117

Hoffend N, Magner W, Tomasi T. The modulation of Dicer regulates tumor immunogenicity in melanoma. Oncotarget 2016; 7: 47663–47673. DOI: https://doi.org/10.18632/oncotarget.10273

Faber C, Horst D, Hlubek F, Kirchner T. Overexpression of Dicer predicts poor survival in colorectal cancer. Euro J Cancer 2011; 47: 1414–1419. DOI: https://doi.org/10.1016/j.ejca.2011.01.006

Caffrey E, Wall D, Webber M, Dinneen K, Ingoldsby H, Murillo L, et al. Prognostic significance of deregulated Dicer expression in breast cancer. PloS One 2013; 231: S32. DOI: https://doi.org/10.1371/journal.pone.0083724

NCCN Clinical practice guidelines in oncology (NCCN Guidelines) melanoma: cutaneous version 2. 2025 January 28. Available from: https://www.nccn.org/login?ReturnURL=https://www.nccn.org/professionals/physician_gls/pdf/cutaneous_melanoma.pdf

Shannon AB, Sharon CE, Straker RJ, Carr MJ, Sinnamon AJ, Bogatch K, et al. Sentinel lymph node biopsy in patients with T1a cutaneous malignant melanoma: a multicenter cohort study. J Am Acad Dermatol 2023; 88: 52–59. DOI: https://doi.org/10.1016/j.jaad.2022.09.040

Del Fiore P, Russo I, Ferrazzi B, Monico AD, Cavallin F, Filoni A, et al. Melanoma in adolescents and young adults: evaluation of the characteristics, treatment strategies, and prognostic factors in a monocentric retrospective study. Front Oncol 2021; 11: 725523. DOI: https://doi.org/10.3389/fonc.2021.725523

Linos E, Swetter SM, Cockburn MG, Colditz GA, Clarke CA. Increasing burden of melanoma in the United States. J Invest Dermatol 2009; 129: 1666–1674. DOI: https://doi.org/10.1038/jid.2008.423

Didier A, Nandwani S, Watkins D, Fahoury A, Campbell A, Craig D, et al. Patterns and trends in melanoma mortality in the United States, 1999–2020. BMC Cancer 2024; 24: 790. DOI: https://doi.org/10.1186/s12885-024-12426-z

Helgadottir H, Mikiver R, Schultz K, Nielsen K, Portelli F, Lapins J, et al. Melanoma incidence and mortality trends among patients aged 59 years or younger in Sweden. JAMA Dermatol 2024; 160: 1201–1210. DOI: https://doi.org/10.1001/jamadermatol.2024.3514

Gómez-Cabello D, Callejas S, Benguría A, Moreno A, Alonso J, Palmero I. Regulation of the MicroRNA processor DGCR8 by the tumor suppressor ING1. Cancer Res 2010; 70: 1866–1874. DOI: https://doi.org/10.1158/0008-5472.CAN-09-2088

Barricklow Z, DiVincenzo M, Angell C, Carson W. Ulcerated cutaneous melanoma: a review of the clinical, histologic, and molecular features associated with a clinically aggressive histologic phenotype. Clin Cosmet Investig Dermatol 2022; 15: 1743–1757. DOI: https://doi.org/10.2147/CCID.S372287

Tokumaru S, Suzuki M, Yamada H, Nagino M, Takahashi T. let-7 regulates Dicer expression and constitutes a negative feedback loop. Carcinogenesis 2008; 29: 2073–2077. DOI: https://doi.org/10.1093/carcin/bgn187

Published

2026-01-08

How to Cite

Schafer, F., Bellolio, E., Sepúlveda, T., Espinoza, M., Orellana, J.-J., Villaseca, M. A., & Miranda, R. (2026). Risk Factors for Melanoma Survival: DGCR8 as a Predictive Factor for Mortality in Young Patients. Acta Dermato-Venereologica, 106, adv44513. https://doi.org/10.2340/actadv.v106.44513

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