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Prediction of Melanoma

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Causes, Screening and Diagnosis".

Deadline for manuscript submissions: 31 January 2026 | Viewed by 4265

Special Issue Editor


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Guest Editor
1st Department of Dermatology, Andreas Syggros Hospital, Medical School, National and Kapodistrian University of Athens, 16121 Athens, Greece
Interests: melanoma; genetic epidemiology; skin cancer syndromes; psoriasis

Special Issue Information

Dear Colleagues,

In recent years, the management of melanoma has undergone profound changes. Targeted therapy, immunotherapy and combinations of these have revolutionized neo-adjuvant, adjuvant therapy, and the treatment of advanced disease. The roller coaster of therapeutics is gaining new speeds, as trials of personalized mRNA vaccines combined with immunotherapy show promising results in reducing the risk of recurrence, while adoptive cell therapy with tumor-infiltrating lymphocytes (TILs) achieves durable responses in advanced disease. Despite these new and exciting advances that set the paradigm for cancer treatment, melanoma remains the most lethal skin malignancy, accounting for tens thousands of deaths each year. What is more, new treatment modalities come at a substantial financial cost and considerable potential toxicities. It is therefore clinically relevant to enhance our ability to predict disease occurrence and progression and offer a tailor-made approach to our patients.

In this regard, the search for methods improving melanoma prediction and for the discovery and validation of new biomarkers is constantly ongoing. AI-based techniques are being incorporated in non-invasive imaging tools, facilitating prediction through reconstructed deep convolutional neural network (CNN) architecture and optimized algorithms. Some of these models use pathological data from dermatoscopic images and incorporate individual patient characteristics for better prediction. Risk prediction tools for melanoma development, recurrence, progression, therapeutic outcome, and survival are already publicly available. Data from genome-wide association studies (GWASs) and whole-exome sequencing studies (WESs) unravel genetic loci conferring genetic susceptibility, enhancing the effort to stratify disease risk. In addition, transcriptome-wide association studies (TWASs) help to identify prognostic markers for tumorigenesis and progression, while the use of gene expression profiling (GEP) in melanoma is still debated. Circulating tumor DNA (ctDNA) is an emerging biomarker that can serve as a noninvasive liquid biopsy for the evaluation of treatment response and the early detection of disease recurrence. Recently, a novel prognostic model in melanoma based on chemokines-related gene signatures has been developed.

Further research and validation of these new developments are required before they are implemented into routine clinical practice. 

Dr. Irene Stefanaki
Guest Editor

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Keywords

  • melanoma
  • melanoma genetics
  • biomarkers
  • predictive tools
  • risk prediction
  • risk factors
  • artificial intelligence

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Published Papers (3 papers)

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Research

20 pages, 2912 KB  
Article
Integrative Molecular and Immune Profiling in Advanced Unresectable Melanoma: Tumor Microenvironment and Peripheral PD-1+ CD4+ Effector Memory T-Cells as Potential Markers of Response to Immune Checkpoint Inhibitor Therapy
by Manuel Molina-García, María Jesús Rojas-Lechuga, Teresa Torres Moral, Francesca Crespí-Payeras, Jaume Bagué, Judit Mateu, Nikolaos Paschalidis, Vinícius Gonçalves de Souza, Sebastian Podlipnik, Cristina Carrera, Josep Malvehy, Rui Milton Patricio da Silva-Júnior and Susana Puig
Cancers 2025, 17(12), 2022; https://doi.org/10.3390/cancers17122022 - 17 Jun 2025
Cited by 1 | Viewed by 1209
Abstract
Background/Objectives: Immune checkpoint inhibitors (ICIs) have revolutionized advanced melanoma treatment, yet many patients fail to achieve sustained clinical benefit. Several biomarkers, including tumor microenvironment (TME) signature, PD-1/PD-L1 expression, and IFN-γ signaling, have been proposed. However, robust predictive markers remain elusive. This study aimed [...] Read more.
Background/Objectives: Immune checkpoint inhibitors (ICIs) have revolutionized advanced melanoma treatment, yet many patients fail to achieve sustained clinical benefit. Several biomarkers, including tumor microenvironment (TME) signature, PD-1/PD-L1 expression, and IFN-γ signaling, have been proposed. However, robust predictive markers remain elusive. This study aimed to identify molecular markers of response by analyzing tumor and peripheral immune signatures. Methods: This study analyzed 21 advanced melanoma patients treated with ICIs. Formalin-fixed, paraffin-embedded tumors underwent RNA-sequencing targeting 1392 immuno-oncology probes. Genes significantly associated with progression-free survival (PFS) by log-rank test underwent hierarchical clustering analysis (HCA). Differential expression and xCell analyses were then performed on the resulting clusters. Cox multivariate analysis was applied to identify independent PFS predictors. Pre-treatment peripheral blood mononuclear cells were analyzed by mass cytometry, followed by FlowSOM and UMAP clustering. Results: Fifty-five genes significantly associated with PFS identified two molecular clusters via HCA. Cluster A demonstrated prolonged PFS (59.4 vs. 2.4 months, p = 0.0004), while Cluster B was characterized by downregulated IFN-γ signaling, antigen presentation pathways, and reduced immune score. Multivariate Cox analysis confirmed molecular cluster as an independent PFS predictor (p < 0.001). Mass cytometry revealed higher frequencies of circulating PD-1+ CD4+ effector memory (EM) T subpopulations among responders. Conclusions: This study highlights the potential role of molecular and immune profiling in predicting ICI response in advanced melanoma. The identification of distinct molecular clusters underscores significant TME heterogeneity, with immune-cold tumor clusters associated with poorer outcomes. Furthermore, circulating PD-1+ T subpopulations emerged as potential markers of ICI response, suggesting their value in improving patient stratification. Full article
(This article belongs to the Special Issue Prediction of Melanoma)
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12 pages, 6258 KB  
Article
A Comparative Study Between Copy Number Alterations and PRAME Immunohistochemical Pilot Study in Challenging Melanocytic Lesions
by Jeana Chun, Ashley R. Scholl, Jennifer Crimmins, Michelle M. Schneider, M. Angelica Selim and Rami N. Al-Rohil
Cancers 2025, 17(7), 1218; https://doi.org/10.3390/cancers17071218 - 4 Apr 2025
Viewed by 758
Abstract
Introduction: Diagnostic uncertainty for ambiguous lesions that fall on the spectrum between nevi and melanoma remains a significant challenge and can have consequences for patient management. Methods: This study aimed to compare the diagnostic utility of preferentially expressed antigen in melanoma (PRAME) immunohistochemistry [...] Read more.
Introduction: Diagnostic uncertainty for ambiguous lesions that fall on the spectrum between nevi and melanoma remains a significant challenge and can have consequences for patient management. Methods: This study aimed to compare the diagnostic utility of preferentially expressed antigen in melanoma (PRAME) immunohistochemistry to molecular testing (FISH and SNP array) in 34 diagnostically challenging melanocytic lesions and 9 non-diagnostically challenging melanomas. Results: We conclude that while PRAME immunohistochemistry demonstrates high specificity (96.2%) in diagnostically challenging melanocytic lesions, its low sensitivity (12.5%) suggests that it should not replace histopathological evaluation in rendering the final diagnosis. Conclusions: These findings suggest that PRAME may serve as a useful adjunct in the diagnostic workup, particularly due to its high negative predictive value, but should be used in conjunction with other established diagnostic modalities. Full article
(This article belongs to the Special Issue Prediction of Melanoma)
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15 pages, 5995 KB  
Article
Distinct Transcriptomic and Tumor Microenvironment Profiles in Sinonasal Mucosal Melanoma and Aggressive Cutaneous Melanomas
by Manuel Molina-García, María Jesús Rojas-Lechuga, Teresa Torres Moral, Jaume Bagué, Judit Mateu, Cristóbal Langdon, Joan Lop, Vinícius Gonçalves de Souza, Llúcia Alós, Mauricio López-Chacón, Sebastian Podlipnik, Cristina Carrera, Josep Malvehy, Isam Alobid, Rui Milton Patricio da Silva-Júnior and Susana Puig
Cancers 2024, 16(24), 4172; https://doi.org/10.3390/cancers16244172 - 14 Dec 2024
Cited by 3 | Viewed by 1624
Abstract
Background/Objectives: Sinonasal mucosal melanoma (SNMM) is a rare and aggressive melanoma subtype with a notably poor prognosis compared to cutaneous melanoma (CM). Despite advances in molecular characterization, SNMM remains underexplored, posing a clinical challenge and highlighting the need for detailed molecular profiling. [...] Read more.
Background/Objectives: Sinonasal mucosal melanoma (SNMM) is a rare and aggressive melanoma subtype with a notably poor prognosis compared to cutaneous melanoma (CM). Despite advances in molecular characterization, SNMM remains underexplored, posing a clinical challenge and highlighting the need for detailed molecular profiling. This study aimed to identify the molecular features of SNMM, elucidate its clinical behavior and prognostic implications, and provide insights for improved therapeutic strategies. Methods: This retrospective study analyzed 37 primary melanoma tumors diagnosed at the Hospital Clinic of Barcelona. Gene expression was examined using 1402 immuno-oncology-related probes through next-generation sequencing. Hierarchical clustering analysis (HCA), differentially expressed genes (DEGs), gene set enrichment analysis (GSEA), and the xCell algorithm were performed. The statistical methods comprised descriptive statistics, clinical variable associations, and survival analyses. Results: HCA revealed two primary clusters. Cluster A exclusively contained CM tumors (20/24), while cluster B included all SNMMs (13/13) and some CMs (4/24). Cluster B showed a higher average age at diagnosis (p = 0.018), higher mitotic index (p = 0.0478), fewer BRAF mutations (p = 0.0017), and poorer melanoma-specific survival (p = 0.0029). Cluster B showed 602 DEGs with cell cycle pathways enriched, immune pathways diminished, lower immune scores (p < 0.0001), and higher stromal scores (p = 0.0074). Conclusions: This study revealed distinct molecular characteristics and an altered tumor microenvironment in SNMMs and certain aggressive CMs. Identifying specific genes and pathways involved in cell cycle progression and immune evasion suggests potential prognostic markers, offering new avenues for enhancing treatment strategies and improving patient survival rates. Full article
(This article belongs to the Special Issue Prediction of Melanoma)
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