Serum MYCN as a predictive biomarker of prognosis and therapeutic response in the prevention of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a deathly cancer with increasing global deaths in the past 20 years. Acyclic retinoid (ACR) is an oral vitamin A derivative showing promising efficacy and safety in clinical studies for preventing HCC recurrence. In this study, tissue and blood-based biomarker analyses were applied to examine the role of MYCN as a predictive biomarker for prognosis of HCC and therapeutic response to ACR. Data mining in The Cancer Genome Atlas database showed that MYCN gene expression was up-regulated in 39.9% of HCC patients, with a shorter median survival time than those with a low MYCN gene expression (37.77 vs 80.7 months). In a validation study, MYCN gene expression in HCC tumors were positively correlated with the recurrence of early stage HCC without cirrhosis or with single tumor. In a proof of concept study, serum MYCN protein levels were significantly higher in HCC patients and decreased after surgical resection for HCC. In a retrospective analysis of phase 3 trial of ACR (N=68), serum MYCN was identified as the risk factor mostly associated with HCC recurrence. HCC patients with a lower serum MYCN levels after a 4-week treatment period had a significantly lower risk of recurrence in ACR group, but not in placebo group. In summary, serum MYCN holds promise for the biomarker-based precise medicine in the prevention of HCC.