title: Inflammation factors in hepatoblastoma and their clinical significance as diagnostic and prognostic biomarkers.
abstract: OBJECTIVE
  The aims of this study were to identify inflammation factors in hepatoblastoma tissue that correlated with different clinical characteristics, and to explore the probability as predictive biomarkers for diagnosis and prognosis.
  
  
  METHODS
  SELDI-TOF-MS was performed to screen protein peaks that were significantly highly expressed in tumor tissue compared with adjacent liver tissue. After removing proteins larger than 30kDa, the targeted peaks were separated by solid phase extraction and tricine-SDS-PAGE. Protein fragments produced by in-gel digestion were identified by LC-MS/MS. Immunohistochemical assays further confirmed these results. Overall survival curves were graphed by Kaplan-Meier method and multivariate analysis was performed by Cox proportional hazards regression model.
  
  
  RESULTS
  Three protein peaks (m/z 12,138, m/z 13,462, and m/z 15,120) that were significantly upregulated in the tumor tissue were identified as macrophage migration inhibitory factor (MIF), chemokine (C-X-C motif) ligand 7 (CXCL7), and interleukin 25 (IL-25). These factors were closely related to clinical stage, lymph node metastasis, vascular invasion and serum AFP level. High expression of each inflammatory marker indicated poor prognosis. Multivariate analysis suggested that MIF, CXCL7, and IL-25 were prognostic factors independent of patient sex, age and tumor histological type.
  
  
  CONCLUSIONS
  MIF, CXCL7, and IL-25 might be considered as effective inflammation factors for diagnosis and prognosis of hepatoblastoma and as potential novel treatment targets through inhibition of inflammatory function.
  
  
  METHODS
  Prognosis study LEVEL OF EVIDENCE: Level I.
authors.affiliation: Department of Pediatric Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, PR China.
authors.forename: Fei
authors.initials: F
authors.lastname: Guo
authors.affiliation: Record Room, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang 453000, Henan, PR China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Ru
authors.affiliation: Department of Pediatric Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, PR China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Psychiatry, Shanghai Mental Health Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, PR China.
authors.forename: Shen
authors.initials: S
authors.lastname: He
authors.affiliation: Institute of Cancer, the Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310000, Zhejiang, PR China.
authors.forename: Jiekai
authors.initials: J
authors.lastname: Yu
authors.affiliation: Institute of Cancer, the Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310000, Zhejiang, PR China.
authors.forename: Shu
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Department of Pediatric Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, PR China. Electronic address: drwangjx@163.com.
authors.forename: Jiaxiang
authors.initials: J
authors.lastname: Wang
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood; D053179:Caspase 7 / Q000097:blood*; D005260:Female; D018197:Hepatoblastoma / Q000175:diagnosis / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D020381:Interleukin-17 / Q000097:blood*; D019746:Intramolecular Oxidoreductases / Q000097:blood*; D008113:Liver Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008263:Macrophage Migration-Inhibitory Factors / Q000097:blood*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D014408:Biomarkers, Tumor; D020381:Interleukin-17; D008263:Macrophage Migration-Inhibitory Factors; D053179:Caspase 7; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human
keywords: CXCL7; IL-25; MIF; Prognosis; Proteomics