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

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.

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.

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).

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.