Diagnostic and Prognostic Roles of Serum Osteopontin and Osteopontin Promoter Polymorphisms in Hepatitis B-related Hepatocellular Carcinoma

  • Chimparlee, Nitinan (Research Unit of Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University) ;
  • Chuaypen, Natthaya (Research Unit of Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University) ;
  • Khlaiphuengsin, Apichaya (Research Unit of Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University) ;
  • Pinjaroen, Nutcha (Department of Radiology, Faculty of Medicine, Chulalongkorn University) ;
  • Payungporn, Sunchai (Research Unit of Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University) ;
  • Poovorawan, Yong (Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University) ;
  • Tangkijvanich, Pisit (Research Unit of Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University)
  • Published : 2015.11.04


Background: The aims of this study were to evaluate the diagnostic and prognostic roles of serum osteopontin (OPN) and single nucleotide polymorphisms (SNPs) in the OPN promoter in patients with hepatitis B-related hepatocellular carcinoma (HCC). Materials and Methods: Four groups were studied, which included 157 patients with HCC, 73 with liver cirrhosis (LC) and 97 with chronic hepatitis (CH), along with 80 healthy subjects. Serum OPN and alpha-fetoprotein (AFP) levels were measured. The SNPs -66 T/G, -156 G/${\Delta}G$ and -433 C/T within the OPN promoter were determined by direct sequencing. Results: Serum OPN levels were significantly higher in patients with HCC than in the other groups. Area under receiver operating characteristics curves in distinguishing HCC from chronic liver disease (CLD; CH and LC) were 0.782 (95% CI; 0.729-0.834) for OPN and 0.888 (95% CI; 0.850-0.927) for AFP. Using the optimal cut-off value (70 ng/mL), OPN had sensitivity and specificity of 72% and 71%, respectively. Serum OPN was superior to AFP in detecting early-stage HCC (68% vs. 46%). A combination of both markers yielded an improved sensitivity for detecting early HCC to 82%. A high OPN level was significantly correlated with advanced BCLC stage and was an independent prognostic factor for HCC. The SNPs -156 and -443 were associated with susceptibility to HCC, but were not related to overall survival. Conclusions: Serum OPN is a useful diagnostic and prognostic marker for HCC. The combined use of serum OPN and AFP improved the diagnosis of early HCC. Genetic variation in the OPN promoter is associated with the risk, but not the prognosis of HCC.


Osteopontin;alpha-fetoprotein;tumor marker;liver cancer;hepatitis B;polymorphisms


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