title: Global Proteome Changes in Liver Tissue 6 Weeks after FOLFOX Treatment of Colorectal Cancer Liver Metastases.
abstract: (1) Oxaliplatin-based chemotherapy for colorectal cancer liver metastasis is associated with sinusoidal injury of liver parenchyma. The effects of oxaliplatin-induced liver injury on the protein level remain unknown. (2) Protein expression in liver tissue was analyzed-from eight patients treated with FOLFOX (combination of fluorouracil, leucovorin, and oxaliplatin) and seven controls-by label-free liquid chromatography mass spectrometry. Recursive feature elimination-support vector machine and Welcht-test were used to identify classifying and relevantly changed proteins, respectively. Resulting proteins were analyzed for associations with gene ontology categories and pathways. (3) A total of 5891 proteins were detected. A set of 184 (3.1%) proteins classified the groups with a 20% error rate, but relevant change was observed only in 55 (0.9%) proteins. The classifying proteins were associated with changes in DNA replication (p< 0.05) through upregulation of the minichromosome maintenance complex and with the innate immune response (p< 0.05). The importance of DNA replication changes was supported by the results of Welcht-test (p< 0.05). (4) Six weeks after FOLFOX treatment, less than 1% of identified proteins showed changes in expression associated with DNA replication, cell cycle entry, and innate immune response. We hypothesize that the changes remain after recovery from FOLFOX treatment injury.
authors.affiliation: Department of Surgical Sciences, Uppsala University, SE-75185 Uppsala, Sweden. jozef.urdzik@surgsci.uu.se.
authors.forename: Jozef
authors.initials: J
authors.lastname: Urdzik
authors.affiliation: Department of Pharmacy, Uppsala University, SE-75237 Uppsala, Sweden. Anna.Vildhede@pfizer.com.
authors.forename: Anna
authors.initials: A
authors.lastname: Vildhede
authors.affiliation: Department of Proteomics and Signal Transduction, Max-Planck-Institute of Biochemistry, Martinsried 82152, Germany. jwisniew@biochem.mpg.de.
authors.forename: Jacek R
authors.initials: JR
authors.lastname: Wiśniewski
authors.affiliation: Department of Surgical Sciences, Uppsala University, SE-75185 Uppsala, Sweden. frans.duraj@surgsci.uu.se.
authors.forename: Frans
authors.initials: F
authors.lastname: Duraj
authors.affiliation: Department of Surgical Sciences, Uppsala University, SE-75185 Uppsala, Sweden. ulf.haglund@akademiska.se.
authors.forename: Ulf
authors.initials: U
authors.lastname: Haglund
authors.affiliation: Department of Pharmacy, Uppsala University, SE-75237 Uppsala, Sweden. per.artursson@farmaci.uu.se.
authors.forename: Per
authors.initials: P
authors.lastname: Artursson
authors.affiliation: Department of Surgical Sciences, Uppsala University, SE-75185 Uppsala, Sweden. agneta.noren@akademiska.se.
authors.forename: Agneta
authors.initials: A
authors.lastname: Norén
keywords: DNA replication; innate immune response; label-free liquid chromatography mass spectrometry; minichromosome maintenance complex; oxaliplatin-based chemotherapy; protein expression; recovery of liver injury