engleski

Proteomic signatures associated with BRAF V600E mutation in colorectal cancer

BRAF V600E–mutated colorectal cancer (CRC) represents a subset of colorectal cancer with distinct clinicopathological features, poor prognosis and limited response to standard chemotherapy regimens. Better understanding of the molecular and cellular processes regulated by BRAF V600E mutation could help to identify potential novel drug targets to increase treatment efficacy in CRC. In the present study, we set out to identify novel potential protein biomarkers associated with aggressive phenotype of BRAF-mutated CRC. Towards this aim, we carried out global proteomic profiling of human colon cancer cells harbouring BRAF V600E mutation vs. BRAF wild-type colon cancer cells using two-dimensional gel electrophoresis (pH ranges 3-10NL and 4-7) followed by MALDI- TOF/TOF mass spectrometric analysis. We detected 99 differentially expressed protein spots between BRAF V600E mutant and BRAF wild- type cells, among which 20 protein spots had statistically significant (p<0.05) differences in the expression levels. The most important downregulated proteins were cyclin-dependent kinase-like 3, WNT1-inducible-signaling pathway protein 3, hexokinase 1 and Ras-related protein Rab-40A, whereas upregulated proteins included MORN repeat-containing protein 5, zinc finger protein 230, eukaryotic elongation factor 2 kinase and serine/threonine-protein kinase 40. Further studies in human tissue samples from CRC patients are warranted to confirm the role of these proteins in the pathogenesis of BRAF V600E-mutated CRC and to investigate their potential prognostic and therapeutic relevance.

colorectal caricnoma, BRAF, mutation, 2-DE, mass spectrometry

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