Back to Search
Start Over
Proteomic phenotyping of metastatic melanoma reveals putative signatures of MEK inhibitor response and prognosis.
- Source :
- British Journal of Cancer; Sep2018, Vol. 119 Issue 6, p713-723, 11p, 1 Chart, 5 Graphs
- Publication Year :
- 2018
-
Abstract
- <bold>Background: </bold>Genotyping of melanomas is used to identify patients for treatment with BRAF and MEK inhibitors, but clinical responses are highly variable. This study investigated the utility of protein expression phenotyping to provide an integrated assessment of gene expression programs in BRAF/NRAS melanoma which would be useful for prognosis and may predict response to MEK inhibition.<bold>Methods: </bold>Mass spectrometry profiling of early passage cell lines established from Stage III cutaneous melanomas was conducted. Basal protein expression was correlated with in vitro response to the MEK inhibitor, selumetinib. Protein expression in a cohort of 32 drug naïve BRAF/NRAS metastatic melanoma specimens was examined. The prognostic utility of a subset of these proteins and mRNA transcripts from a separate cohort was determined.<bold>Results: </bold>Unsupervised analysis of basal cell line protein abundances delineated response to selumetinib, but BRAF/NRAS genotype did not. Resistance was associated with functions including cell motility, cell adhesion and cytoskeletal organization. Several of these response biomarkers were observed in lymph node biospecimens and correlated with melanoma-specific survival. Loss of ICAM-1 protein and mRNA expression was a strong prognosticator of diminished survival in BRAF/NRAS mutant melanoma.<bold>Conclusions: </bold>These results demonstrate the utility of proteomic phenotyping to identify both putative biomarkers of response to MEK inhibition and prognostication associated with metastatic melanoma. [ABSTRACT FROM AUTHOR]
- Subjects :
- RESEARCH
GENETIC mutation
MELANOMA
HETEROCYCLIC compounds
LIQUID chromatography
PROTEIN kinase inhibitors
RESEARCH methodology
PROGNOSIS
EVALUATION research
MEDICAL cooperation
PROTEOMICS
SKIN tumors
HYDROLASES
TUMOR classification
COMPARATIVE studies
TRANSFERASES
SURVIVAL analysis (Biometry)
MASS spectrometry
CELL lines
MEMBRANE proteins
ANTIGENS
LONGITUDINAL method
Subjects
Details
- Language :
- English
- ISSN :
- 00070920
- Volume :
- 119
- Issue :
- 6
- Database :
- Complementary Index
- Journal :
- British Journal of Cancer
- Publication Type :
- Academic Journal
- Accession number :
- 132187547
- Full Text :
- https://doi.org/10.1038/s41416-018-0227-2