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Proteomes 2016, 4(4), 30; doi:10.3390/proteomes4040030

Global Proteome Changes in Liver Tissue 6 Weeks after FOLFOX Treatment of Colorectal Cancer Liver Metastases

1
Department of Surgical Sciences, Uppsala University, SE-75185 Uppsala, Sweden
2
Department of Pharmacy, Uppsala University, SE-75237 Uppsala, Sweden
3
Department of Proteomics and Signal Transduction, Max-Planck-Institute of Biochemistry, Martinsried 82152, Germany
Current affiliation: Pharmacokinetics Dynamics and Metabolism, Pfizer Global Research and Development, Pfizer Inc., Groton, CT 06340, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Dariusz Rakus
Received: 17 August 2016 / Revised: 6 October 2016 / Accepted: 7 October 2016 / Published: 14 October 2016
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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 Welch t-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 Welch t-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. View Full-Text
Keywords: oxaliplatin-based chemotherapy; protein expression; label-free liquid chromatography mass spectrometry; DNA replication; minichromosome maintenance complex; innate immune response; recovery of liver injury oxaliplatin-based chemotherapy; protein expression; label-free liquid chromatography mass spectrometry; DNA replication; minichromosome maintenance complex; innate immune response; recovery of liver injury
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Urdzik, J.; Vildhede, A.; Wiśniewski, J.R.; Duraj, F.; Haglund, U.; Artursson, P.; Norén, A. Global Proteome Changes in Liver Tissue 6 Weeks after FOLFOX Treatment of Colorectal Cancer Liver Metastases. Proteomes 2016, 4, 30.

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