Circulating Clusterin Levels and Cancer Risk: A Systematic Review and Meta-Analysis

INTRODUCTION: The previous reports on clusterin (CLU) levels in various types of cancer have been controversial and heterogeneous. The present meta-analysis has aimed to evaluate the association between soluble CLU levels and the risk of different human cancers based on observational studies. METHODS: A systematic literature review was conducted to determine the relevant eligible studies in English language from health-related electronic databases up to January 2021. Random effects models were used to calculate the summary standard mean difference (SMD) with 95% confidence intervals (CIs) to identify the correlation between CLU levels and cancer risk. The meta-regression, sensitivity, Galbraith, and subgroup analyses were performed to explore the source of between-study heterogeneity. Furthermore, the funnel plot and Egger’s linear regression tests were carried out to evaluate the risk of publication bias. RESULTS: According to 16 eligible articles, 3331 patients and 839 healthy controls were included in our meta-analysis. Overall, the CLU levels were significantly higher in various cancer cases compared to the healthy groups (SMD = 1.50, 95% CI = 0.47–2.53). Moreover, subgroup analysis based on types of cancer showed a significant correlation between CLU levels and the risk of digestive system cancers (SMD = 1.54, 95% CI = 0.91–2.18, P <0.001), especially in HCC (SMD = 1.89, 95% CI = 0.76–3.03, P = 0.001), and CRC (SMD = 1.63, 95% CI = 0.0–3.23, P = 0.048). CONCLUSION: The present meta-analysis indicates a significant association of CLU levels with the risk of digestive system cancers such as hepatocellular carcinoma and colorectal cancer. Therefore, CLU can be monitored as a novel molecular biomarker for the prognosis and diagnosis of various types of cancers particularly in the digestive system.