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A 3D Organotypic Melanoma Spheroid Skin Model
Published on: May 18, 2018
Risk Factors for Melanoma Survival: DGCR8 as a Predictive Factor for Mortality in Young Patients
Fabiola Schafer1, Enrique Bellolio2, Tatiana Sepúlveda2
1Department of Medical Specialties, School of Medicine, Universidad de La Frontera, Temuco, Chile. fdschafe@gmail.com.
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.
Insights
DGCR8, a microRNA-processing enzyme, may predict mortality risk in melanoma patients. Positive DGCR8 expression indicates higher mortality risk, especially in younger patients, aiding in stratifying high-risk individuals.
Area of Science:
- Oncology
- Molecular Biology
- Biomarker Discovery
Background:
- MicroRNA-processing enzymes, Dicer and DGCR8, are dysregulated in melanoma.
- Melanoma progression and patient survival are influenced by microRNA pathways.
Purpose of the Study:
- To investigate DGCR8 and Dicer as potential risk factors for melanoma mortality.
- To evaluate the utility of these enzymes in stratifying patient risk.
Main Methods:
- Retrospective cohort study of 74 melanoma patients.
- Immunohistochemistry used to assess DGCR8 and Dicer expression (%IRC).
- Dichotomous expression (negative/positive) based on an 80% IRC cut-off.
Main Results:
- Stage III-IV melanoma patients had a 5-year survival rate of 18.5%.
- Positive DGCR8 expression was a significant predictor of mortality in patients aged ≤42 years (HR=14.3, p=0.024).
- Multivariate analysis identified positive DGCR8 and younger age (≤42) as associated with lower survival in stage III-IV melanoma.
Conclusions:
- DGCR8 expression may serve as a novel biomarker for melanoma patient mortality.
- DGCR8 positivity can help identify high-risk melanoma patients, particularly younger individuals.
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