Quantitative Proteomic Analysis Identified Paraoxonase 1 as a Novel Serum Biomarker for Microvascular Invasion in Hepatocellular Carcinoma

This study aimed to identify serum biomarkers for microvascular invasion (MVI) in hepatocellular carcinoma (HCC). MVI is a histological sign of micrometastasis in the liver and is considered as one of the most powerful prognostic factors in HCC. The serum of HCC patients with different vascular invasion statuses was examined by iTRAQ-based proteomic profiling. The expression levels of 24 proteins were associated with the extent of vascular invasion in the pooled samples of 45 HCC cases. Western blot analyses in 90 HCC cases confirmed the correlation of the expression level of paraoxonase 1 (PON1) with the extent of vascular invasion. ELISA assays demonstrated the diagnostic utility of the PON1 level, with the area under curve values of 0.847 and 0.889 for the MVI and gross vascular invasion, respectively, relative to the patients without vascular invasion, in a cohort of 387 additional HCC cases. Immunohistochemistry revealed that PON1 expression in tumor cells was inversely correlated with the extent of vascular invasion in 200 additional HCC cases. In conclusion, using a proteomic approach, we found that serum PON1 was a novel diagnostic biomarker for MVI. The prognostic values of serum PON1 and its possible therapeutic applications are worth further investigation.