Serum PON1 as a biomarker for the estimation of microvascular invasion in hepatocellular carcinoma.

ABSTRACT

BACKGROUND: Microvascular invasion (MVI) is considered as one of the most powerful prognostic factors in hepatocellular carcinoma (HCC). Currently, it could only be diagnosed by post-operative histological examination. This study aimed to assess the diagnostic value of serum paraoxonase 1 (PON1) for MVI. METHODS: In this study, we analyzed data from 754 HCC patients who underwent surgical treatment between December 2010 and November 2011. Serum PON1 was measured by ELISA and receiver operating characteristic (ROC) curve was applied to calculate diagnostic accuracy. RESULTS: MVI was detected in 174 of 505 patients (34.5%) in the test cohort and 84 of 249 patients (33.7%) in the validation cohort. Univariate analyses indicated tumor size, AFP, and PON1 were significantly related with vascular invasion status. ROC curves determined the optimum diagnostic cutoff value for PON1 was 191.12 ng/mL (AUC 0.754, 95% CI 0.710-0.798, sensitivity 70.67%, specificity 78.11% in the test cohort), which was significantly better than AFP (cutoff value 279.8 ng/mL, AUC 0.666, 95% CI 0.618-0.714, sensitivity 40.38%, specificity 85.19%, P=0.0063). In the sHCC sub-group, PON1 retained diagnostic value (AUC 0.738, 95% CI 0.680-0.796, sensitivity 72.82%, specificity 76.57% in the test cohort), while AFP failed to do so (AUC 0.579, 95% CI 0.511-0.647, sensitivity 26.21%, specificity 86.84%, P=0.0003). These results were further confirmed by the validation cohort. The combination of PON1 and AFP increased the diagnostic accuracy for vascular invasion compared with either test alone (AUC 0.785, 95% CI 0.744-0.826, sensitivity 75.96%, specificity 77.44%; PON1 plus AFP vs. PON1 alone, P=0.0004; PON1 plus AFP vs. AFP alone, P<0.0001). CONCLUSIONS: Serum PON1 could potentially be used to diagnose MVI and could be used to guide more personalized treatment strategy.