PLASMA GLYPICAN-3 AND OSTEOPONTIN IN DIAGNOSING HEPATOCELLULAR CARCINOMA WITH LOW SERUM AFP AND PIVKA II

Abstract

Background: Alphafetoprotein (AFP) is the most widely used biomarker for hepatocellular carcinoma (HCC) surveillance and diagnosis. However, the low sensitivity (66%) and specificity(82%) of AFP in diagnosing HCC led to withdrawal from the recent American HCC guideline that recommended radiological test alone for HCC surveillance. Glypican-3 (GPC3) and Osteopontin (OPN) are secreted glycoproteins known to be associated with tumorigenesis and metastasis, and have been suggested as potential tumor markers for various human tumors. Aim of our study is evaluating the clinical significance of plasma GPC3 and OPN level in HCC patients with low serum AFP and prothrombin induced by vitamin K absence II (PIVKAII)

Methods: From August 2007 to March 2011, total of eighty patients were enrolled. The HCC group comprised 60 patients who were newly diagnosed as HCC with low AFP (≤20ng/mL) and PIVKA II (≤100 mAU/mL). The chronic liver disease (CLD) group included 20 patients with CLD such as chronic hepatitis B (CHB) and liver cirrhosis (LC) without liver cancer. All patients have low levels of serum AFP and PIVKA II. We measured the plasma levels of GPC3 and OPN using commercially available ELISA kit.

Result: In HCC group, mean patient age was 60 years, and 72% were male. CHB was the most common etiology of underlying liver disease (67%). The Child-Pugh class of patients with HCC was class A in 80% and class B in 20%. The mean tumor size was 2.7 cm, and mostly single tumor (77%). The percentage of patients at BCLC stage O, A, B, C and D were 23.8%, 41.3%, 7.5%, 2.5%, and 0%, respectively. Median serum levels of AFP and PIVKA II were 5.2ng/mL and 27.1 mAU/mL, respectively. Plasma GPC3 levels in the HCC group were higher than those in the CLD group (84.8ng/mL vs. 41.2 ng/mL, p=0.002). We found no statistical difference in plasma OPN levels of both group (135.5 ng/mL vs.150.5 ng/mL, p=0.385). The area under the receiver-operating characteristics curve value for GPC3 was 0.731 (95% CI:0.59~0.88) and cut-off level of 75 ng/mL yielded the highest predictive value of diagnosing HCC with sensitivity 61% and specificity 85%.

Conclusion: Our study suggested that the plasma GPC3 is a potential tumor marker for HCC, especially among patients with low serum AFP and PIVKA II.