The causal relationship between cathepsins and hepatocellular carcinoma risk: A Mendelian randomization study

Abstract

Background Abnormal expression of cathepsins has been reported in patients with hepatocellular carcinoma (HCC). However, the evidence about the causal role of cathepsins in facilitating or preventing HCC is lacking. Systematically studying the causality between cathepsins and HCC would help provide novel targets for screening and prevention of HCC. Methods We conducted twosample Mendelian randomization (MR) analyses. The data of cathepsins and HCC for analysis were derived from publicly available genetic summary data. The causal effects were estimated with inverse variance weighted, MR-Egger and weighted median. Sensitivity analyses were implemented with Cochran's Q test, MR-Egger intercept test, MR-PRESSO and leave-one-out analysis. Results The results of univariate MR analysis show that elevated cathepsin S levels increase the risk of HCC. On the other hand, reverse MR analyses indicate that HCC may raise cathepsin Z levels. According to the results of multivariable analysis using nine cathepsin variables, an increased risk of HCC is associated with elevated levels of cathepsin S. Conclusion The evidence that cathepsin S is associated with HCC in a causal way provides a novel insight into the underlying mechanisms of HCC by integrating genomics with cathepsins, and has an implication for HCC screening and prevention.