title: DUSP 4 expression identifies a subset of colorectal cancer tumors that differ in MAPK activation, regardless of the genotype.
abstract: As dual-specificity phosphatase (DUSP) expression has been correlated to sensitivity to MEK inhibitors, DUSP expression levels may indicate activation of the mitogen-activated protein kinase (MAPK) pathway in many tumor types. In this study, we investigate if DUSP levels can indicate different levels of MAPK activation within colorectal cancer (CRC) patients. In three different CRC patient microarray datasets, we analyzed the expression of DUSP1. DUSP4 and DUSP6 according to mutational status, their correlation with survival and their association with different clinical characteristics. DUSP4 was significantly differentially expressed between all mutational subgroups with the highest expression in BRAF mutated tumors. Moreover, high DUSP4 expression was associated with a worse overall survival and with clinical characteristics typical for BRAF mutant patients. The use of DUSP expression as a predictive biomarker towards MAPK targeted therapy in CRC patients needs further investigation.
authors.affiliation: Lab of Molecular Digestive Oncology, Department of Oncology , KULeuven , Belgium .
authors.forename: Veerle
authors.initials: V
authors.lastname: De Vriendt
authors.forename: Wendy
authors.initials: W
authors.lastname: De Roock
authors.forename: Antonio Fabio
authors.initials: AF
authors.lastname: Di Narzo
authors.forename: Sun
authors.initials: S
authors.lastname: Tian
authors.forename: Bart
authors.initials: B
authors.lastname: Biesmans
authors.forename: Bart
authors.initials: B
authors.lastname: Jacobs
authors.forename: Eva
authors.initials: E
authors.lastname: Budinska
authors.forename: Xavier
authors.initials: X
authors.lastname: Sagaert
authors.forename: Simona
authors.initials: S
authors.lastname: Rossi
authors.forename: Giovanni
authors.initials: G
authors.lastname: D'Ario
authors.forename: Mauro
authors.initials: M
authors.lastname: Delorenzi
authors.forename: Iris
authors.initials: I
authors.lastname: Simon
authors.forename: Loredana
authors.initials: L
authors.lastname: Vecchione
authors.forename: Sabine
authors.initials: S
authors.lastname: Tejpar
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000145:classification* / Q000201:enzymology / Q000235:genetics; D054642:Dual Specificity Phosphatase 6 / Q000235:genetics; D054637:Dual-Specificity Phosphatases / Q000235:genetics*; D004789:Enzyme Activation; D005838:Genotype; D006801:Humans; D054639:Mitogen-Activated Protein Kinase Phosphatases / Q000235:genetics*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D020928:Mitogen-Activated Protein Kinases; D054639:Mitogen-Activated Protein Kinase Phosphatases; C490583:DUSP4 protein, human; C517035:DUSP6 protein, human; D054642:Dual Specificity Phosphatase 6; D054637:Dual-Specificity Phosphatases