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

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 I (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 PON I 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 PON I 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/m L., AUC 0.666, 95% CI: 0.618-0.714, sensitivity 40.38%, specificity 85.19%, P=0.0063). In the sHCC sub-group, PONI 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. PONI 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.