Evidence map›Paper›PMID 40075679›Full record

ArticleCancers2025

Proteogenomic Profiling of Treatment-Naïve Metastatic Malignant Melanoma.

Magdalena Kuras, Lazaro Hiram Betancourt, Runyu Hong, Leticia Szadai, Jimmy Rodriguez, Peter Horvatovich, Indira Pla, Jonatan Eriksson, Beáta Szeitz, Bartłomiej Deszcz and 21 more

Abstract read
In one paragraph

Article in Cancers, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

31 authors.

Magdalena KurasDepartment of Translational Medicine, Lund University, Skåne University Hospital Malmö, 214 28 Malmö, Sweden.ORCID 0000-0002-9479-423X
Lazaro Hiram BetancourtDepartment of Translational Medicine, Lund University, Skåne University Hospital Malmö, 214 28 Malmö, Sweden.
Runyu HongInstitute for Systems Genetics, NYU Grossman School of Medicine, New York, NY 10016, USA.
Leticia SzadaiDepartment of Dermatology and Allergology, University of Szeged, 6720 Szeged, Hungary.ORCID 0000-0002-3605-839X
Jimmy RodriguezDepartment of Biochemistry and Biophysics, Karolinska Institute, 171 77 Stockholm, Sweden.
Peter HorvatovichDepartment of Biomedical Engineering, Lund University, 221 00 Lund, Sweden.ORCID 0000-0003-2218-1140
Indira PlaDepartment of Biomedical Engineering, Lund University, 221 00 Lund, Sweden.
Jonatan ErikssonDepartment of Biomedical Engineering, Lund University, 221 00 Lund, Sweden.
Beáta SzeitzDivision of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, 1085 Budapest, Hungary.
Bartłomiej DeszczDepartment of Biochemistry and Microbiology, Warsaw University of Life Sciences, 02-787 Warsaw, Poland.
Charlotte WelinderDepartment of Clinical Sciences Lund, Division of Oncology, Lund University, 221 00 Lund, Sweden.ORCID 0000-0001-9626-0576
Yutaka SugiharaDepartment of Biomedical Engineering, Lund University, 221 00 Lund, Sweden.
Henrik EkedahlDepartment of Clinical Sciences Lund, Division of Oncology, Lund University, 221 00 Lund, Sweden.ORCID 0000-0003-4337-8495
Bo BaldetorpDepartment of Clinical Sciences Lund, Division of Oncology, Lund University, 221 00 Lund, Sweden.
Christian IngvarSUS University Hospital Lund, 222 42 Lund, Sweden.ORCID 0000-0002-7721-4619
Lotta LundgrenDepartment of Clinical Sciences Lund, Division of Oncology, Lund University, 221 00 Lund, Sweden.
Henrik LindbergDepartment of Biomedical Engineering, Lund University, 221 00 Lund, Sweden.
Henriett OskolasDepartment of Clinical Sciences Lund, Division of Oncology, Lund University, 221 00 Lund, Sweden.
Zsolt HorvathDepartment of Biomedical Engineering, Lund University, 221 00 Lund, Sweden.
Melinda RezeliDepartment of Biomedical Engineering, Lund University, 221 00 Lund, Sweden.ORCID 0000-0003-4373-5616
Jeovanis GilDepartment of Translational Medicine, Lund University, Skåne University Hospital Malmö, 214 28 Malmö, Sweden.ORCID 0000-0003-3601-3893
Roger AppelqvistDepartment of Biomedical Engineering, Lund University, 221 00 Lund, Sweden.ORCID 0000-0001-7450-7216
Lajos V KeményHCEMM-SU Translational Dermatology Research Group, Semmelweis University, 1085 Budapest, Hungary.
Johan MalmDepartment of Translational Medicine, Lund University, Skåne University Hospital Malmö, 214 28 Malmö, Sweden.ORCID 0000-0002-9365-7313
Aniel SanchezDepartment of Translational Medicine, Lund University, Skåne University Hospital Malmö, 214 28 Malmö, Sweden.ORCID 0000-0002-0278-8802
Attila Marcell SzaszDepartment of Bioinformatics, Semmelweis University, 1085 Budapest, Hungary.ORCID 0000-0003-2739-4196
Krzysztof PawłowskiDepartment of Translational Medicine, Lund University, Skåne University Hospital Malmö, 214 28 Malmö, Sweden.
Elisabet WieslanderDepartment of Translational Medicine, Lund University, Skåne University Hospital Malmö, 214 28 Malmö, Sweden.
David FenyöInstitute for Systems Genetics, NYU Grossman School of Medicine, New York, NY 10016, USA.ORCID 0000-0001-5049-3825
Istvan Balazs NemethDepartment of Dermatology and Allergology, University of Szeged, 6720 Szeged, Hungary.
György Marko-VargaDepartment of Biomedical Engineering, Lund University, 221 00 Lund, Sweden.

Funding

Proteogenomic Data Analysis for Cancer Systems Biology and Clinical TranslationU24CA210972 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI DING, LI, FENYO, DAVID · 2016 to 2020
$3.3M
Berta Kamprad Foundation FBKS-2023-22-99Berta Kamprad Foundation IKEA FBKS-2024-19 - 604Hungarian Academy of Sciences OTKA-125509Hungarian National Research, Development and Innovation Office OTKA FK138696National Cancer Institute (NCI) CPTAC grant U24CA210972National Research, Development and Innovation Fund (Hungary) ÚNKP-21-3- SZTE-102National Research, Development and Innovation Fund (Hungary) ÚNKP-22-3-IINCI NIH HHS U24 CA210972Semmelweis 250+ Excellence Ph.D. Scholarship EFOP-3.6.3-VEKOP-16-2017-00009Semmelweis University grant STIA-KFI2021
6 · The paper itself

Abstract

backgroundMelanoma is a highly heterogeneous disease, and a deeper molecular classification is essential for improving patient stratification and treatment approaches. Here, we describe the histopathology-driven proteogenomic landscape of 142 treatment-naïve metastatic melanoma samples to uncover molecular subtypes and clinically relevant biomarkers.

methodsWe performed an integrative proteogenomic analysis to identify proteomic subtypes, assess the impact of BRAF V600 mutations, and study the molecular profiles and cellular composition of the tumor microenvironment. Clinical and histopathological data were used to support findings related to tissue morphology, disease progression, and patient outcomes.

resultsOur analysis revealed five distinct proteomic subtypes that integrate immune and stromal microenvironment components and correlate with clinical and histopathological parameters. We demonstrated that BRAF V600-mutated melanomas exhibit biological heterogeneity, where an oncogene-induced senescence-like phenotype is associated with improved survival. This led to a proposed mortality risk-based stratification that may contribute to more personalized treatment strategies. Furthermore, tumor microenvironment composition strongly correlated with disease progression and patient outcomes, highlighting a histopathological connective tissue-to-tumor ratio assessment as a potential decision-making tool. We identified a melanoma-associated SAAV signature linked to extracellular matrix remodeling and SAAV-derived neoantigens as potential targets for anti-tumor immune responses.

conclusionsThis study provides a comprehensive stratification of metastatic melanoma, integrating proteogenomic insights with histopathological features. The findings may aid in the development of tailored diagnostic and therapeutic strategies, improving patient management and outcomes.

Indexed as

BRAF V600Ehistopathologylymph node metastasesmelanomaproteogenomicsproteomicssingle amino acid variantsstratificationsubtypestumor microenvironment

Identifiers

PMID40075679
PMCPMC11899103

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.