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Imaging Mass Spectrometry for the Classification of Melanoma Based on BRAF / NRAS Mutational Status
Ist Teil von
International journal of molecular sciences, 2023-03, Vol.24 (6), p.5110
Ort / Verlag
Switzerland: MDPI AG
Erscheinungsjahr
2023
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
Mutations of the oncogenes v-raf murine sarcoma viral oncogene homolog B1 (
) and neuroblastoma RAS viral oncogene homolog (
) are the most frequent genetic alterations in melanoma and are mutually exclusive.
V600 mutations are predictive for response to the two
inhibitors vemurafenib and dabrafenib and the mitogen-activated protein kinase kinase (MEK) inhibitor trametinib. However, inter- and intra-tumoral heterogeneity and the development of acquired resistance to
inhibitors have important clinical implications. Here, we investigated and compared the molecular profile of
and
mutated and wildtype melanoma patients' tissue samples using imaging mass spectrometry-based proteomic technology, to identify specific molecular signatures associated with the respective tumors. SCiLSLab and R-statistical software were used to classify peptide profiles using linear discriminant analysis and support vector machine models optimized with two internal cross-validation methods (leave-one-out, k-fold). Classification models showed molecular differences between
and
mutated melanoma, and identification of both was possible with an accuracy of 87-89% and 76-79%, depending on the respective classification method applied. In addition, differential expression of some predictive proteins, such as histones or glyceraldehyde-3-phosphate-dehydrogenase, correlated with
or
mutation status. Overall, these findings provide a new molecular method to classify melanoma patients carrying
and
mutations and help provide a broader view of the molecular characteristics of these patients that may help understand the signaling pathways and interactions involving the altered genes.