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Independent replication of a melanoma subtype gene signature and evaluation of its prognostic value and biological correlates in a population cohort

Lookup NU author(s): Dr Jérémie Nsengimana

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

Development and validation of robust molecular biomarkers has so far been limited in melanoma research. In this paper we used a large population-based cohort to replicate two published gene signatures for melanoma classification. We assessed the signatures prognostic value and explored their biological significance by correlating them with factors known to be associated with survival (vitamin D) or etiological routes (nevi, sun sensitivity and telomere length). Genomewide microarray gene expressions were profiled in 300 archived tumors (224 primaries, 76 secondaries). The two gene signatures classified up to 96% of our samples and showed strong correlation with melanoma specific survival (P=3x10-4), Breslow thickness (P=5x10-10), ulceration (P=9.x10-8) and mitotic rate (P=3x10-7), adding prognostic value over AJCC stage (adjusted hazard ratio 1.79, 95%CI 1.13-2.83), as previously reported. Furthermore, molecular subtypes were associated with seasonadjusted serum vitamin D at diagnosis (P=0.04) and genetically predicted telomere length (P=0.03). Specifically, molecular high-grade tumors were more frequent in patients with lower vitamin D levels whereas high immune tumors came from patients with predicted shorter telomeres. Our data confirm the utility of molecular biomarkers in melanoma prognostic estimation using tiny archived specimens and shed light on biological mechanisms likely to impact on cancer initiation and progression.

Publication metadata

Author(s): Nsengimana J, Laye J, Filia A, Walker C, Jewell R, Van Den Oord JJ, Wolter P, Patel P, Sucker A, Schadendorf D, Jonsson GB, Bishop DT, Newton-Bishop J

Publication type: Article

Publication status: Published

Journal: Oncotarget

Year: 2015

Volume: 6

Issue: 13

Pages: 11683-11693

Online publication date: 12/03/2015

Acceptance date: 10/02/2015

Date deposited: 11/06/2020

ISSN (electronic): 1949-2553

Publisher: Impact Journals LLC

URL: https://doi.org/10.18632/oncotarget.3549

DOI: 10.18632/oncotarget.3549

PubMed id: 25871393

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