Clinicopathological and prognostic significance of high Ki-67 labeling index in hepatocellular carcinoma patients: a meta-analysis

Background: The relationship between Ki-67 labeling index (LI) and clinical outcome in hepatocellular carcinoma (HCC) has been investigated by various studies, but no consistent result has been concluded. To define the prognostic significance of Ki-67 LI in patients with HCC, we performed a meta-analysis. Methods: We searched for literatures in the following databases: PubMed, ISI Web of Science, EMBASE, Cochrane Central Register of Controlled Trials, Science Direct, Wiley Online Library, Google Scholar, China National Knowledge Infrastructure (CNKI), Chinese VIP and WanFang Databases. Our search ended on April 6th, 2015. Data were extracted from eligible studies and the correlation between Ki-67 LI and clinicopathological features of HCC was analyzed and pooled hazard ratios (HRs) for eligible studies were calculated by STATA 11.0 (STATA Corp., College, TX). Results: In total, 54 studies involving 4996 patients were included in the current meta-analysis. The meta-analysis provided evidence that high Ki-67 LI was closely associated with histological grade, tumor size, number of tumor nodes, the status of metastasis, cirrhosis and vein invasion in HCC patients. The pooled HRs showed that high Ki-67 LI had an unfavorable impact on disease-free survival (DFS) (HR=1.626, 95% confidence interval (CI): 1.364-1.939, P<0.001), relapse-free survival (RFS) (HR=1.820, 95% CI: 1.215-2.725, P=0.004) and overall survival (OS) (HR=1.170, 95% CI: 1.102-1.243, P<0.001), respectively. Additionally, subgroup analysis indicated that high Ki-67 LI was related to poorer DFS, RFS and OS independent of regions, treatment strategies or statistical methods, except that no statistical significance was found on RFS (HR=2.413, 95% CI: 0.523-11.142, P=0.259) and OS (HR=1.998, 95% CI: 0.797-5.009, P=0.14) in patients with liver transplantation. Conclusions: Our meta-analysis suggests that higher Ki-67 LI confers a fast progression and poor prognosis for HCC patients.