SUOX is a promising diagnostic and prognostic biomarker for hepatocellular carcinoma

• Published in: Journal of hepatology Vol. 59; no. 3; pp. 510 - 517
• Main Authors: Jin, Guang-Zhi, Yu, Wen-Long, Dong, Hui, Zhou, Wei-Ping, Gu, Yi-Jin, Yu, Hao, Yu, Hua, Lu, Xin Yuan, Xian, Zhi-Hong, Liu, Yin-Kun, Cong, Wen-Ming, Wu, Meng-Chao
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.09.2013
• Subjects: Aldehyde Reductase - metabolism; Aldo-keto reductase family 1 member B10; alpha-Fetoproteins - metabolism; Antigens, CD34 - metabolism; Biomarkers, Tumor - metabolism; Carcinoma, Hepatocellular - diagnosis; Carcinoma, Hepatocellular - enzymology; Carcinoma, Hepatocellular - pathology; CD34; Cohort Studies; Diagnosis; Diagnosis, Differential; Female; Gastroenterology and Hepatology; High grade dysplastic nodules; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Liver - metabolism; Liver - pathology; Liver Neoplasms - diagnosis; Liver Neoplasms - enzymology; Liver Neoplasms - pathology; Logistic Models; Male; Middle Aged; Oxidoreductases Acting on Sulfur Group Donors - metabolism; Prognosis; Sulfite oxidase; Well-differentiated small hepatocellular carcinoma; Aldo-keto reductase family 1 member B10; Prognosis; hepatitis B virus; DN; time to recurrence; sulfite oxidase; AFP; TTR; overall survival; α-fetoprotein; Diagnosis; receiver operating characteristic; HBV; CD34; hepatocellular carcinoma; WD-sHCC; well-differentiated small hepatocellular carcinoma; OS; high-grade dysplastic nodules; ROC; HGDN; HCC; SUOX; dysplastic nodules; AKR1B10; MD-sHCC; aldo-ketoreductase family 1 member B10; High grade dysplastic nodules; moderately differentiated HCC; Well-differentiated small hepatocellular carcinoma; Sulfite oxidase
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/j.jhep.2013.04.028

Background & Aims 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.