Dataset Information

Proteogenomics linked to histopathology identifies subtypes and progression biomarkers in malignant melanoma

ABSTRACT: In this study, proteogenomic analysis coupled with clinical histopathology revealed proteomic subtypes and identified candidate markers, which uncovered tumor biology related to patient survival. A total of 12,695 proteins and 45,356 phosphosites were quantified. This newly generated proteomic data was integrated with a previously published transcriptomic dataset from matched tumor specimens (Cirenajwis et al., 2015). Using consensus clustering, we could identify five melanoma subtypes, which were classified into extracellular, extracellular-immune, mitochondrial, mitochondrial-immune, and extracellular-mitochondrial categories according to/based on the annotations of their highly expressed proteins. The proteomic subtypes displayed differences in phenotype switching, immune surveillance, the levels of known melanoma markers, and were associated with survival. In addition, clinical parameters such as the expression of mutated BRAF V600E protein and the composition of the surrounding tumor microenvironment were found to be good independent indicators of prognosis. Lastly, validation of survival-related proteins in an independent cohort identified five candidate markers for predicting disease progression and patient survival (ADAM10, SCAI, CTNND1, CDK4, FGA). In conclusion, this study provides insights into the complex biology of melanoma while emphasizing/highlighting the importance of the tumor microenvironment. It also offers opportunities to find/indentify novel drug target candidates.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Melanocyte, Lymph Node

SUBMITTER: Magdalena Kuras

LAB HEAD: György Marko-Varga

PROVIDER: PXD035206 | Pride | 2025-05-06

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	20180509_MM_TMT_B1_61min_R1.raw	Raw
	20180509_MM_TMT_B1_F19_R1.raw	Raw
	20180509_MM_TMT_B1_F23_R1.raw	Raw
	20180509_MM_TMT_B2_F10_R1.raw	Raw
	20180509_MM_TMT_B2_F11_R1.raw	Raw

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Publications

Proteogenomic Profiling of Treatment-Naïve Metastatic Malignant Melanoma.

Kuras Magdalena M Betancourt Lazaro Hiram LH Hong Runyu R Szadai Leticia L Rodriguez Jimmy J Horvatovich Peter P Pla Indira I Eriksson Jonatan J Szeitz Beáta B Deszcz Bartłomiej B Welinder Charlotte C Sugihara Yutaka Y Ekedahl Henrik H Baldetorp Bo B Ingvar Christian C Lundgren Lotta L Lindberg Henrik H Oskolas Henriett H Horvath Zsolt Z Rezeli Melinda M Gil Jeovanis J Appelqvist Roger R Kemény Lajos V LV Malm Johan J Sanchez Aniel A Szasz Attila Marcell AM Pawłowski Krzysztof K Wieslander Elisabet E Fenyö David D Nemeth Istvan Balazs IB Marko-Varga György G

Cancers 20250227 5

<h4>Background</h4>Melanoma 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.<h4>Methods</h4>We performed an integrative proteogenomic analysis to identify proteomic subtypes, assess the impact of BRAF V600 mutations ...[more]

PMID: 40075679

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