Long-term prognostic impact of osteopontin and Dickkopf-related protein 1 in patients with hepatocellular carcinoma after hepatectomy

Background

New biomarkers are essential for improving the prediction of the survival and prognosis of patients with hepatocellular carcinoma (HCC). Alpha-fetoprotein (AFP) is the most widely used biomarker, but the low sensitivity and specificity limit its clinical applications. The diagnostic and prognostic capabilities of osteopontin (OPN), dickkopf-related protein 1 (DKK1), and a combination of these biomarkers are being studied.

Methods

From January 2006 to December 2008, patients undergoing hepatectomy for HCC were screened and their serum stored in tumor banks was analyzed. The serum was used to investigate OPN and DKK1 levels by enzyme-linked immunosorbent assay(ELISA). In the paraffin block, the status of OPN and DKK1 positivity was assessed using immunohistochemistry(IHC).

Results

A total of 60 patients were enrolled. The optimal cut-off level for survival was identified as 3.0?ng/mL and 5.2?ng/mL of OPN and DKK1, respectively. In multivariate analysis, a high OPN level was the only significant prognostic factor for overall survival hazard ratio3.79, p?=?.017]. Considering a combination of AFP (cut-off level, 200?ng/mL) and OPN/DKK1, the patients with high AFP and OPN/DKK1 levels showed significantly lower overall survivals than those with low AFP, high AFP, and low OPN/DKK1 levels (p?=?.0091 for the AFP and OPN group, p?=?.0344 for the AFP and DKK1 group). Comparison between IHC and ELISA results for OPN and DKK1 levels did not reveal any significant correlation.

Conclusions

Serum OPN and DKK1 levels of HCC patients could be considered as novel biomarkers showing prognostic significance after hepatectomy based on long-term survival data.