The Clinicopathological and Prognostic Significance of P27 in Hepatocellular Carcinoma Patients: A Systemic Review and Meta-analysis

Objectives: P27 is a cyclin-dependent kinase inhibitor that has gained importance as a biomarker in human malignant tumors. However, the potential role of P27 in hepatocellular carcinoma remains unclear. The aim of this meta-analysis was to explore whether P27 acts as prognostic and clinicopathological roles in hepatocellular carcinoma patients.

Methods/materials: An electronic search based on three databases, PubMed, Embase, and Web of Science, was performed to select a sufficient number of studies. Pooled hazard ratio (HR) and odds ratio (OR) were used as estimates to investigate the association among P27 expression, prognosis and clinicopathological features.

Results: In total, we identified 18 studies with 1774 hepatocellular carcinoma patients. The result derived from four studies revealed a significant positive association between lower P27 levels and shorter overall survival (HR = 0.550, 95% CI: 0.464-0.652, P < 0001) and disease-free survival (HR = 0.420, 95% CI: 0.308-0.571, P < 0.0001). Analyses of the clinicopathological features and P27 expression also showed that a positive rate of P27 was significantly lower in a larger sized tumor (OR = 0.538, 95% CI: 0.315-0.919, P = 0.023). The results also revealed that lower P27 levels were correlated with poorer differentiation (0.416, 95% CI: 0.178-0.971, P = 0.043). Additionally, the pooled OR of 0.389 also presented a significant correlation between P27 underexpression and the metastasis of HCCs (95% CI: 0.155-0.975, P = 0.044).

Conclusions: This analysis suggests a strong association among P27 underexpression, poorer prognosis and aggressive progression of hepatocellular carcinoma in patients. P27 may be a tumor suppressor for predicting the progression and survival outcome in patients with hepatocellular carcinomas.