High Copy Number Variations Correlate with a Pro-Tumoral Microenvironment and Worse Prognosis in Acral Lentiginous Melanoma

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dc.contributor.authorde la Rosa, Inés
dc.contributor.authorSisó Camarasa, Pol
dc.contributor.authorRíos, Christopher
dc.contributor.authorGracia, Judith
dc.contributor.authorCuevas Sánchez, Dolors
dc.contributor.authorMaiques Carlos, Oscar
dc.contributor.authorEritja Sánchez, Núria
dc.contributor.authorSoria, Xavier
dc.contributor.authorÀngel Baldó, Joan
dc.contributor.authorGatius Calderó, Sònia
dc.contributor.authorSanchez-Moral, Lidia
dc.contributor.authorSarrias, Maria-Rosa
dc.contributor.authorMatias-Guiu, Xavier
dc.contributor.authorMartí Laborda, Rosa Ma.
dc.contributor.authorMacià Armengol, Anna
dc.date.accessioned2025-09-02T07:42:50Z
dc.date.available2025-09-02T07:42:50Z
dc.date.issued2025-04-25
dc.date.updated2025-09-02T07:42:50Z
dc.description.abstractAcral 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.
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.3390/ijms26094097
dc.identifier.idgrec035664
dc.identifier.issn1661-6596
dc.identifier.urihttps://hdl.handle.net/10459.1/468510
dc.language.isoeng
dc.publisherMDPI
dc.relation.isformatofReproducció del document publicat a: https://doi.org/10.3390/ijms26094097
dc.relation.ispartofInternational Journal Of Molecular Sciences, 2025, vol. 26, num. 9, p. 4097
dc.rightscc-by (c) de la Rosa, Inés et al., 2025
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectAcral lentiginous melanoma
dc.subjectCopy number variation
dc.subjectTumor microenvironment
dc.subjectSecretome
dc.subjectPrognosis
dc.titleHigh Copy Number Variations Correlate with a Pro-Tumoral Microenvironment and Worse Prognosis in Acral Lentiginous Melanoma
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/publishedVersion
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