High Copy Number Variations Correlate with a Pro-Tumoral Microenvironment and Worse Prognosis in Acral Lentiginous Melanoma
Acral lentiginous melanoma (ALM) is a rare melanoma subtype primarily located in acral regions. However, ALMs exhibit a distinctive genetic profile characterized by a high number of copy number variations (CNVs) and limited point mutations. Late diagnosis and restricted therapeutic efficacy contribute to its poor prognosis. The secretome within the tumor microenvironment (TME) influences immune modulation and plays a vital role in melanoma progression. We aim to analyze the role of ALM secretome and CNVs profile with prognosis in primary ALM patients. Here, we demonstrated that high CNV burden (CNVsHigh) was associated with worse clinicopathological characteristics and poor prognosis. Furthermore, our study also revealed that conditioned media (CM) of CNVsHigh genetic profile ALM cell line was associated with pro-tumoral, pro-angiogenic, and immunosuppressive secretome profiles. In addition, CM of CNVsHigh cell lines in vitro promotes macrophage polarization to immunosuppressive phenotype. Moreover, we observed an increased presence of immunosuppressive tumor-associated macrophages (TAMs) at the invasive front (IF) of CNVsHigh ALM biopsies. This research reveals the adverse prognostic impact of CNVsHigh in ALM patients, establishing a novel link with a pro-tumor secretome, offering potential biomarkers for prognosis and personalized treatment to enhanced disease monitoring in ALM patients.
Authors
- Maria‐Rosa Sarrias (ORCID: https://orcid.org/0000-0001-6929-8069)
- Pol Sisó (ORCID: https://orcid.org/0000-0002-3079-1793)
- Anna Macià (ORCID: https://orcid.org/0000-0001-6038-178X)
- Óscar Maiques (ORCID: https://orcid.org/0000-0002-2172-4388)
- Dolors Cuevas (ORCID: https://orcid.org/0000-0002-2318-4012)
- Manuel Martín González (ORCID: https://orcid.org/0000-0001-6866-6114)
- Xavier Matías‐Guiu (ORCID: https://orcid.org/0000-0002-7201-6605)
- Núria Eritja (ORCID: https://orcid.org/0000-0003-1018-6649)
- Inés de la Rosa
- Sónia Gatius (ORCID: https://orcid.org/0000-0002-1636-6010)
- Lidia Sánchez-Moral (ORCID: https://orcid.org/0000-0002-3795-8015)
- Christopher Ríos (ORCID: https://orcid.org/0009-0008-3902-1593)
- X. Soria (ORCID: https://orcid.org/0000-0002-5644-1214)
- J Angel-Baldo
Institutions
- Institute of Cancer Research (GB)
- Universitat de Lleida (ES)
- Queen Mary University of London (GB)
- Breast Cancer Now (GB)
- Instituto de Salud Carlos III (ES)
- Hospital Universitari Arnau de Vilanova (ES)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (ES)
- Instituto de Investigación Biomédica de Lleida (ES)
- Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol (ES)
- Centro de Investigación Biomédica en Red de Cáncer (ES)
Publication Details
- Journal
- International Journal of Molecular Sciences
- Published
- 2025-04-25
- DOI
- https://doi.org/10.3390/ijms26094097
- Citations
- 1
- Primary Topic
- Cutaneous Melanoma Detection and Management
- Type
- article
- Field-Weighted Citation Impact
- 1.05
Funders
- Centres de Recerca de Catalunya
- European Commission
- Generalitat de Catalunya
- Universitat de Lleida
- Xarxa de Bancs de Tumors de Catalunya
- Agència de Gestió d'Ajuts Universitaris i de Recerca
- Instituto de Salud Carlos III
- European Regional Development Fund