Introduction : Cereblon is a substrate receptor of the E3 ubiquitin ligase complex and functions as a metabolic regulator, directly interacting with AMP-activated protein kinase (AMPK) α1 and inhibiting AMPK activation.

Methods : We developed CRBN-specific monoclonal primary antibody to detect cereblon at the tissue samples (patent). After immunocytochemical staining and Western blot assay, cereblon was quantitatively measured. We performed two development cohort studies to find out the role of cereblon as prognostic biomarker for hepatocellular carcinoma (HCC). Its cutoff was set to be 2 folds comparing with non-tumorous tissue.

Results : One development cohort included 40 patients who underwent macroscopic curative resection for HCC of 7th AJCC stage I or II. The profiles of patients in stage I and II groups were similar each other. There was no significant difference in tumor recurrence (p=0.14) and patient survival (p=0.33) between the stage I and II groups. Higher cereblon expression was observed in 19 (47.5%). High cereblon expression group showed higher recurrence (p=0.017) and lower survival (p=0.025) rates than low cereblon expression group. The hazard ratio of cereblon was estimated to 3.5 (p=0.035). Another development cohort study for response treatment to sorafenib was performed, in which cereblon does not appear to be a reliable response biomarker so far.

Conclusions : The post-resection prognostic impact of cereblon was greater than that of microvascular invasion in solitary HCCs. We think that cereblon can be an independent biomarker to predict post-resection prognosis even in patients with early HCCs. Further high-volume validation study is necessary to investigate the role of cereblon in HCC.