The clinicopathological and prognostic significance of P27^kip in hepatocellular carcinoma patients: A systemic review and meta-analysis.

OBJECTIVES:P27^kip is a cyclin-dependent kinase inhibitor that has gained importance as a biomarker in human malignant tumors. However, the potential role of P27^kip in hepatocellular carcinoma remains unclear. The aim of this meta-analysis was to explore whether P27^kip 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^kip 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^kip 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^kip expression also showed that a positive rate of P27^kip 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^kip 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^kip underexpression and the metastasis of HCCs (95% CI: 0.155-0.975, P = 0.044). CONCLUSIONS:This analysis suggests a strong association among P27^kip underexpression, poorer prognosis and aggressive progression of hepatocellular carcinoma in patients. P27^kip may be a tumor suppressor for predicting the progression and survival outcome in patients with hepatocellular carcinomas.

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