Transcriptomic Analysis Reveals Prognostic Molecular Signatures of Stage I Melanoma

• Published in: Clinical cancer research Vol. 25; no. 24; pp. 7424 - 7435
• Main Authors: Thakur, Rohit, Laye, Jonathan P., Lauss, Martin, Diaz, Joey Mark S., O'Shea, Sally Jane, Poźniak, Joanna, Filia, Anastasia, Harland, Mark, Gascoyne, Joanne, Randerson-Moor, Juliette A., Chan, May, Mell, Tracey, Jönsson, Göran, Bishop, D. Timothy, Newton-Bishop, Julia, Barrett, Jennifer H., Nsengimana, Jérémie
• Format: Journal Article
• Language: English
• Published: United States 15.12.2019
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor - genetics; Cancer and Oncology; Cancer och onkologi; Clinical Medicine; Cohort Studies; Computational Biology - methods; Female; Gene Expression Regulation, Neoplastic; Humans; Immunotherapy - mortality; Klinisk medicin; Male; Medical and Health Sciences; Medicin och hälsovetenskap; Melanoma - genetics; Melanoma - pathology; Melanoma - therapy; Melanoma, Cutaneous Malignant; Middle Aged; Neoplasm Staging; Skin Neoplasms - genetics; Skin Neoplasms - pathology; Skin Neoplasms - therapy; Survival Rate; Transcriptome; Treatment Outcome; Young Adult
• ISSN: 1078-0432; 1557-3265; 1557-3265
• DOI: 10.1158/1078-0432.CCR-18-3659

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. 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. Previous Lund and The Cancer Genome Atlas signatures predicted outcome in the LMC dataset ( = 10 to 10 ) but showed a significant interaction with AJCC stage ( = 0.04) and did not predict outcome in stage I tumors ( = 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 and expression and evidence of epithelial-to-mesenchymal transition. A transcriptomic signature of primary melanoma was identified with prognostic value, including in stage I melanoma and in patients undergoing immunotherapy.