To investigate the expression level and clinical significance of paraoxonase 2 (PON2) in hepatocellular carcinoma (HCC).

Through analyzing data from TCGA database and cBioPortal database, evaluating the correlation between PON2 mRNA expression level and clinicopathological characteristics as well as prognosis, a nomogram was developed that integrated critical variables. To validate PON2 expression at protein level, immunohistochemical staining was performed in 89 human HCC tissue samples and its correlation with clinicopathological characteristics was analyzed briefly.

The expression level of PON2 mRNA was correlated with age (P=0.038), tumor grade (P=0.005), AFP level (P=0.003), adjacent hepatic tissue inflammation (P=0.001) and overall survival event (P=0.027) in HCC patients. Kaplan-Meier analysis showed that high expression of PON2 mRNA predicted shorter overall survival than low expression group (P=0.004). Nomogram demonstrated high accuracy C-index of 0.723 (95% CI: 0.708-0.737, P<0.05) in predicting the 1-, 3- and 5-year overall survival of HCC patients. Immunohistochemistry further showed that PON2 protein expression was 65.2% in high expression HCC tissues. High PON2 protein expression was significantly positively associated with tumor stage (P<0.001) and tumor grade (P<0.001) in HCC patients, as well as significantly related to vascular invasion (P=0.035), overall survival event (P=0.019) and recurrence (P=0.002).

PON2 expression is significantly elevated in HCC and correlated with diagnosis and poor prognosis. The nomogram model, including PON2 mRNA and several key factors, is of high precision and provides valuable guidance for clinical decision-making.