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Transcriptomic Analysis Reveals Prognostic Molecular Signatures of Stage I Melanoma

Lookup NU author(s): Dr Jérémie Nsengimana

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Abstract

©2019 American Association for Cancer Research.Purpose: Previously identified transcriptomic signatures have been based on primary and metastatic melanomas with relatively few American Joint Committee on Cancer (AJCC) stage I tumors, given difficulties in sampling small tumors. The advent of adjuvant therapies has highlighted the need for better prognostic and predictive biomarkers, especially for AJCC stage I and stage II disease. Experimental Design: A total of 687 primary melanoma transcriptomes were generated from the Leeds Melanoma Cohort (LMC). The prognostic value of existing signatures across all the AJCC stages was tested. Unsupervised clustering was performed, and the prognostic value of the resultant signature was compared with that of sentinel node biopsy (SNB) and tested as a biomarker in three published immunotherapy datasets. Results: Previous Lund and The Cancer Genome Atlas signatures predicted outcome in the LMC dataset (P = 10¯8 to 10¯4) but showed a significant interaction with AJCC stage (P = 0.04) and did not predict outcome in stage I tumors (P = 0.3–0.7). Consensus-based classification of the LMC dataset identified six classes that predicted outcome, notably in stage I disease. LMC class was a similar indicator of prognosis when compared with SNB, and it added prognostic value to the genes reported by Gerami and colleagues. One particular LMC class consistently predicted poor outcome in patients receiving immunotherapy in two of three tested datasets. Biological characterization of this class revealed high JUN and AXL expression and evidence of epithelial-to-mesenchymal transition. Conclusions: A transcriptomic signature of primary melanoma was identified with prognostic value, including in stage I melanoma and in patients undergoing immunotherapy.

Publication metadata

Author(s): Thakur R, Laye JP, Lauss M, Diaz JMS, O'Shea SJ, Poźniak J, Filia A, Harland M, Gascoyne J, Randerson-Moor JA, Chan M, Mell T, Jönsson G, Timothy Bishop D, Newton-Bishop J, Barrett JH, Nsengimana J

Publication type: Article

Publication status: Published

Journal: Clinical Cancer Research

Year: 2019

Volume: 25

Issue: 24

Pages: 7424-7435

Online publication date: 01/12/2019

Acceptance date: 29/08/2019

ISSN (print): 1078-0432

ISSN (electronic): 1557-3265

Publisher: American Association for Cancer Research Inc.

URL: https://doi.org/10.1158/1078-0432.CCR-18-3659

DOI: 10.1158/1078-0432.CCR-18-3659

PubMed id: 31515461

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