title: SUOX is a promising diagnostic and prognostic biomarker for hepatocellular carcinoma.
abstract: OBJECTIVE
  To investigate diagnostic and prognostic values of sulfite oxidase (SUOX) in patients with hepatocellular carcinoma (HCC) who underwent curative resection.
  
  
  METHODS
  We investigated immunohistochemically the expression dynamics of SUOX, aldo-ketoreductase family 1 member B10 (AKR1B10) and CD34 at different stages of HCC. The differential diagnostic performance of three markers or their combinations in high-grade dysplastic nodules (HGDNs) and well-differentiated small HCC (WD-sHCC) were investigated by logistic regression models and validated in an independent testing set. Overall survival (OS) and time to recurrence (TTR) were evaluated in 300 patients with HCC as the testing cohort, and validated in 198 patients with HCC.
  
  
  RESULTS
  SUOX was decreased and AKR1B10 and CD34 were increased with the stepwise progression of hepatocarcinogenesis. For differential diagnosis of WD-sHCC from HGDNs, the sensitivity and specificity of the SUOX+AKR1B10+CD34 combination for WD-sHCC detection were 93.8% and 95.2%, respectively, and overall accuracy was much higher than any of the three individual markers and two marker combinations. In addition, SUOX, but not AKR1B10 and CD34, was an independent prognostic factor for OS and TTR, and showed better correlation with OS and TTR if combined with serum α-fetoprotein (AFP) for both the testing and validation cohorts.
  
  
  CONCLUSIONS
  SUOX+AKR1B10+CD34 combination could make a substantial contribution to hepatic immunopathological diagnosis to distinguish WD-sHCC from HGDNs. Meanwhile, SUOX combined with serum AFP may predict postoperative outcome and tumor recurrence risk.
authors.affiliation: Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.
authors.forename: Guang-Zhi
authors.initials: GZ
authors.lastname: Jin
authors.forename: Wen-Long
authors.initials: WL
authors.lastname: Yu
authors.forename: Hui
authors.initials: H
authors.lastname: Dong
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Zhou
authors.forename: Yi-Jin
authors.initials: YJ
authors.lastname: Gu
authors.forename: Hao
authors.initials: H
authors.lastname: Yu
authors.forename: Hua
authors.initials: H
authors.lastname: Yu
authors.forename: Xin Yuan
authors.initials: XY
authors.lastname: Lu
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Xian
authors.forename: Yin-Kun
authors.initials: YK
authors.lastname: Liu
authors.forename: Wen-Ming
authors.initials: WM
authors.lastname: Cong
authors.forename: Meng-Chao
authors.initials: MC
authors.lastname: Wu
mesh_terms: D000449:Aldehyde Reductase / Q000378:metabolism; D000074408:Aldo-Keto Reductases; D018952:Antigens, CD34 / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000201:enzymology* / Q000473:pathology; D015331:Cohort Studies; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000201:enzymology* / Q000473:pathology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D050862:Oxidoreductases Acting on Sulfur Group Donors / Q000378:metabolism*; D011379:Prognosis; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: C097353:AFP protein, human; D018952:Antigens, CD34; D014408:Biomarkers, Tumor; D000509:alpha-Fetoproteins; C120471:AKR1B10 protein, human; D000074408:Aldo-Keto Reductases; D000449:Aldehyde Reductase; D050862:Oxidoreductases Acting on Sulfur Group Donors; C503599:SUOX protein, human
keywords: AFP; AKR1B10; Aldo-keto reductase family 1 member B10; CD34; DN; Diagnosis; HBV; HCC; HGDN; High grade dysplastic nodules; MD-sHCC; OS; Prognosis; ROC; SUOX; Sulfite oxidase; TTR; WD-sHCC; Well-differentiated small hepatocellular carcinoma; aldo-ketoreductase family 1 member B10; dysplastic nodules; hepatitis B virus; hepatocellular carcinoma; high-grade dysplastic nodules; moderately differentiated HCC; overall survival; receiver operating characteristic; sulfite oxidase; time to recurrence; well-differentiated small hepatocellular carcinoma; α-fetoprotein