OPN is a promising serological biomarker for hepatocellular carcinoma diagnosis.

Hepatocellular carcinoma (HCC) accounts for 90% of cases of liver cancer and is one of the most common and lethal malignancies among all cancers. Current screening practices in high-risk populations using ultrasound and serological α-fetoprotein (AFP) have significantly reduced HCC mortality. However, considering the highly operative-dependent nature of ultrasound and dissatisfactory diagnostic performance of AFP, there is an unfulfilled need for a biomarker that can be used in HCC-related at-risk population screening. Here, sera from 322 patients, including 105 cases of chronic hepatitis (CH), 116 of liver cirrhosis (LC), and 101 of HCC, were collected. Two biomarkers, osteopontin (OPN) and dickkopf WNT signaling pathway inhibitor 1 (DKK1), were evaluated and compared with AFP alone and in combination. In our data, the serum OPN level increased significantly in HCC even in tumors of less than 2 cm. The area under the curve (AUC) reached 0.851, much higher than AFP and DKK1, with 79.21% sensitivity and 79.64% specificity at optimal cutoff in all of the samples. In AFP-negative samples, serum OPN also performed well with an AUC of 0.838. The combination of AFP and OPN improved diagnosis performance significantly when compared with AFP alone. However, the DKK1 level showed an increase in HCC only compared with the LC group. The AUC does not improve significantly when added into the binary logistic model. We conclude that OPN, but not DKK1, is a promising biomarker for HCC diagnosis.