Urdzik Jozef, Vildhede Anna, Wiśniewski Jacek R, Duraj Frans, Haglund Ulf, Artursson Per, Norén Agneta
Department of Surgical Sciences, Uppsala University, SE-75185 Uppsala, Sweden.
Department of Pharmacy, Uppsala University, SE-75237 Uppsala, Sweden.
Proteomes. 2016 Oct 14;4(4):30. doi: 10.3390/proteomes4040030.
(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 -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 ( < 0.05) through upregulation of the minichromosome maintenance complex and with the innate immune response ( < 0.05). The importance of DNA replication changes was supported by the results of Welch -test ( < 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.
(1) 基于奥沙利铂的化疗用于结直肠癌肝转移与肝实质的窦状隙损伤相关。奥沙利铂诱导的肝损伤对蛋白质水平的影响尚不清楚。(2) 通过无标记液相色谱质谱法分析了8例接受FOLFOX（氟尿嘧啶、亚叶酸和奥沙利铂联合）治疗的患者及7例对照的肝组织中的蛋白质表达。分别使用递归特征消除支持向量机和韦尔奇检验来识别分类蛋白和相关变化的蛋白。对所得蛋白进行基因本体类别和通路的关联分析。(3) 共检测到5891种蛋白质。一组184种（3.1%）蛋白质以20%的错误率对各组进行了分类，但仅在55种（0.9%）蛋白质中观察到相关变化。这些分类蛋白通过微小染色体维持复合体的上调与DNA复制变化相关（P<0.05），并与先天免疫反应相关（P<0.05）。韦尔奇检验的结果支持了DNA复制变化的重要性（P<0.05）。(4) FOLFOX治疗六周后，不到1%的已鉴定蛋白质显示出与DNA复制、细胞周期进入和先天免疫反应相关的表达变化。我们推测这些变化在从FOLFOX治疗损伤中恢复后仍然存在。
