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PMEL as a Prognostic Biomarker and Negatively Associated With Immune Infiltration in Skin Cutaneous Melanoma (SKCM)
Shuguang Zhang1, Kun Chen2, Huanmei Liu1
1Department of Orthopedics.
Abstract:
Premelanosome protein (PMEL) is crucial for the formation of melanosomal fibrils through the transition from stage I to stage II melanosomes. It was used as a target antigen in some adoptive T-cell therapy of melanoma. The correlation of PMEL to prognosis and immune cell infiltration level are unknown in melanoma. The PMEL expression was evaluated via Tumor Immune Estimation Resource, Oncomine and Gene Expression Profiling Interactive Analysis (GEPIA). We also evaluate the influence of PMEL on overall survival via GEPIA, PrognoScan, and immunohistochemistry in human tissue microarray. The correlation between PMEL expression level and immune cell or gene markers of immune infiltration level was explored on Tumor Immune Estimation Resource and GEPIA. PMEL expression was significantly higher in skin cutaneous melanoma (SKCM) and SKCM-metastasis in comparison with the other cancers. In SKCM, PMEL expression in high levels was associated with poor overall survival. In both SKCM and SKCM-metastasis patients, PMEL expression is negatively correlated with the infiltration cells of CD8+ T cells, macrophages, and neutrophils. Programmed cell-death protein 1 just showed response rates ranging from 20% to 40% in patients with melanoma, so it is critical to discover a new therapeutic target. PMEL is negatively associated with immune cell infiltration and can be as a negative prognosis marker or new immunotherapy target in SKCM and SKCM-metastasis.
Insights
Premelanosome protein (PMEL) is highly expressed in melanoma, correlating with poor survival and reduced immune cell infiltration. This suggests PMEL may be a novel immunotherapy target for melanoma patients.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Premelanosome protein (PMEL) is essential for melanosome development and has been explored as a target antigen in melanoma therapy.
- The prognostic significance and relationship of PMEL expression with immune infiltration in melanoma remain largely uncharacterized.
Purpose of the Study:
- To investigate the correlation of PMEL expression with prognosis and immune cell infiltration in melanoma.
- To evaluate PMEL as a potential negative prognostic marker and novel immunotherapy target in cutaneous melanoma.
Main Methods:
- PMEL expression analysis using public databases: Tumor Immune Estimation Resource (TIMER), Oncomine, and Gene Expression Profiling Interactive Analysis (GEPIA).
- Overall survival analysis via GEPIA, PrognoScan, and immunohistochemistry on human tissue microarrays.
- Exploration of PMEL's correlation with immune cell markers using TIMER and GEPIA.
Main Results:
- PMEL expression was significantly elevated in skin cutaneous melanoma (SKCM) and its metastatic form compared to other cancers.
- High PMEL expression in SKCM was associated with poorer overall survival.
- PMEL expression showed a negative correlation with the infiltration of CD8+ T cells, macrophages, and neutrophils in both SKCM and metastatic SKCM.
Conclusions:
- PMEL expression is a significant negative prognostic marker in SKCM and metastatic SKCM.
- The negative association between PMEL and immune cell infiltration suggests its potential as a novel immunotherapy target for melanoma.
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