1. Comparative Quantitative Proteomic Analysis of Melanoma Subtypes, Nevus-Associated Melanoma, and Corresponding Nevi.
- Author
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Naimy S, Sølberg JBK, Kuczek DE, Løvendorf MB, Bzorek M, Litman T, Mund A, Rahbek Gjerdrum LM, Clark RA, Mann M, and Dyring-Andersen B
- Subjects
- Humans, Female, Male, Middle Aged, Aged, Proteome analysis, Proteome metabolism, Adult, Signal Transduction, Laser Capture Microdissection, Mass Spectrometry, Melanoma, Cutaneous Malignant, Melanoma pathology, Melanoma metabolism, Skin Neoplasms pathology, Skin Neoplasms metabolism, Proteomics methods, Nevus pathology, Nevus metabolism
- Abstract
A substantial part of cutaneous malignant melanomas develops from benign nevi. However, the precise molecular events driving the transformation from benign to malignant melanoma are not well-understood. We used laser microdissection and mass spectrometry to analyze the proteomes of melanoma subtypes, including superficial spreading melanomas (n = 17), nodular melanomas (n = 17), and acral melanomas (n = 15). Furthermore, we compared the proteomes of nevi cells with those of melanoma cells within the same specimens (nevus-associated melanoma (n = 14)). In total, we quantified 7935 proteins. Despite the genomic and clinical differences of the melanoma subtypes, our analysis revealed relatively similar proteomes, except for the upregulation of proteins involved in immune activation in nodular melanomas versus acral melanomas. Examining nevus-associated melanoma versus nevi, we found 1725 differentially expressed proteins (false discovery rate < 0.05). Among these proteins were 140 that overlapped with cancer hallmarks, tumor suppressors, and regulators of metabolism and cell cycle. Pathway analysis indicated aberrant activation of the phosphoinositide 3-kinase-protein kinase B-mTOR pathways and the Hippo-YAP pathway. Using a classifier, we identified six proteins capable of distinguishing melanoma from nevi samples. Our study represents a comprehensive comparative analysis of the proteome in melanoma subtypes and associated nevi, offering insights into the biological behavior of these distinct entities., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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