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Transcriptomic anal...
Transcriptomic analysis reveals prognostic molecular signatures of stage I melanoma
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- Thakur, Rohit (author)
- University of Leeds,University of Texas
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- Laye, Jonathan P. (author)
- University of Leeds
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- Lauss, Martin (author)
- Lund University,Lunds universitet,Melanoma Genomics,Forskargrupper vid Lunds universitet,Lund University Research Groups
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- Diaz, Joey Mark S. (author)
- University of Leeds
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- O'Shea, Sally Jane (author)
- Mater Private Hospital Cork,University College Cork
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- Pozniak, Joanna (author)
- Catholic University of Leuven,University of Leeds
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- Filia, Anastasia (author)
- Academy of Athens
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- Harland, Mark (author)
- University of Leeds
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- Gascoyne, Joanne (author)
- University of Leeds
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- Randerson-Moor, Juliette A. (author)
- University of Leeds
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- Chan, May (author)
- University of Leeds
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- Mell, Tracey (author)
- University of Leeds
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- Jonsson, Goran (author)
- Lund University,Lunds universitet,Lunds Melanomstudiegrupp,Forskargrupper vid Lunds universitet,Melanoma Genomics,Lund Melanoma Study Group,Lund University Research Groups
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- Timothy Bishop, D. (author)
- University of Leeds
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- Newton-Bishop, Julia (author)
- University of Leeds
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- Barrett, Jennifer H. (author)
- University of Leeds
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- Nsengimana, Jeremie (author)
- University of Leeds
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(creator_code:org_t)
- 2019
- 2019
- English 12 s.
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In: Clinical Cancer Research. - 1078-0432. ; 25:24, s. 7424-7435
- Related links:
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
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- art (subject category)
- ref (subject category)
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- By the author/editor
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Thakur, Rohit
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Laye, Jonathan P ...
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Lauss, Martin
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Diaz, Joey Mark ...
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O'Shea, Sally Ja ...
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Pozniak, Joanna
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show more...
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Filia, Anastasia
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Harland, Mark
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Gascoyne, Joanne
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Randerson-Moor, ...
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Chan, May
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Mell, Tracey
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Jonsson, Goran
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Timothy Bishop, ...
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Newton-Bishop, J ...
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Barrett, Jennife ...
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Nsengimana, Jere ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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Clinical Cancer ...
- By the university
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Lund University