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


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-relatedhepatocellular carcinoma (HCC). Materials and
Methods: Four groups were studied, which included 157 patientswith 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/ΔG and -433 C/Twithin the OPN promoter were determined by direct sequencing.
Results: Serum OPN levels were significantlyhigher in patients with HCC than in the other groups. Area under receiver operating characteristics curves indistinguishing HCC from chronic liver disease (CLD; CH and LC) were 0.782 (95% CI; 0.729-0.834) for OPNand 0.888 (95% CI; 0.850-0.927) for AFP. Using the optimal cut-off value (70 ng/mL), OPN had sensitivity andspecificity 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 highOPN level was significantly correlated with advanced BCLC stage and was an independent prognostic factorfor HCC. The SNPs -156 and -443 were associated with susceptibility to HCC, but were not related to overallsurvival.
Conclusions: Serum OPN is a useful diagnostic and prognostic marker for HCC. The combined use ofserum OPN and AFP improved the diagnosis of early HCC. Genetic variation in the OPN promoter is associatedwith the risk, but not the prognosis of HCC.