DUSP 4 expression identifies a subset of colorectal cancer tumors that differ in MAPK activation, regardless of the genotype

Veerle De Vriendt, Wendy De Roock, Antonio Fabio Di Narzo, Sun Tian, Bart Biesmans, Bart Jacobs, Eva Budinska, Xavier Sagaert, Simona Rossi, Giovanni D'Ario, Mauro Delorenzi, Iris Simon, Loredana Vecchione, Sabine Tejpar

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)516-524
Number of pages9
JournalBiomarkers
Volume18
Issue number6
DOIs
Publication statusPublished - Sep 2013

Keywords

  • Colorectal cancer
  • gene expression
  • MAPK pathway

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Health, Toxicology and Mutagenesis

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    De Vriendt, V., De Roock, W., Di Narzo, A. F., Tian, S., Biesmans, B., Jacobs, B., Budinska, E., Sagaert, X., Rossi, S., D'Ario, G., Delorenzi, M., Simon, I., Vecchione, L., & Tejpar, S. (2013). DUSP 4 expression identifies a subset of colorectal cancer tumors that differ in MAPK activation, regardless of the genotype. Biomarkers, 18(6), 516-524. https://doi.org/10.3109/1354750X.2013.819038