Serum MYCN as a predictive biomarker of prognosis and therapeutic response in the prevention of hepatocellular carcinoma recurrence
Journal
International journal of cancer
Date Issued
2024-02-21
Author(s)
Qin, Xian-Yang
Shirakami, Yohei
Honda, Masao
Numata, Kazushi
Lai, Ya-Yun
Li, Chiao-Ling
Wei, Feifei
Xu, Yali
Imai, Kenji
Takai, Koji
Chuma, Makoto
Komatsu, Nagisa
Furutani, Yutaka
Gailhouste, Luc
Aikata, Hiroshi
Chayama, Kazuaki
Enomoto, Masaru
Tateishi, Ryosuke
Kawaguchi, Kazunori
Yamashita, Tatsuya
Kaneko, Shuichi
Nagaoka, Katsuya
Tanaka, Motohiko
Sasaki, Yutaka
Tanaka, Yasuhito
Baba, Hideo
Miura, Kouichi
Ochi, Sae
Masaki, Takahiro
Kojima, Soichi
Matsuura, Tomokazu
Shimizu, Masahito
Moriwaki, Hisataka
Suzuki, Harukazu
Abstract
The proto-oncogene MYCN expression marked a cancer stem-like cell population in hepatocellular carcinoma (HCC) and served as a therapeutic target of acyclic retinoid (ACR), an orally administered vitamin A derivative that has demonstrated promising efficacy and safety in reducing HCC recurrence. This study investigated the role of MYCN as a predictive biomarker for therapeutic response to ACR and prognosis of HCC. MYCN gene expression in HCC was analyzed in the Cancer Genome Atlas and a Taiwanese cohort (N = 118). Serum MYCN protein levels were assessed in healthy controls (N = 15), patients with HCC (N = 116), pre- and post-surgical patients with HCC (N = 20), and a subset of patients from a phase 3 clinical trial of ACR (N = 68, NCT01640808). The results showed increased MYCN gene expression in HCC tumors, which positively correlated with HCC recurrence in non-cirrhotic or single-tumor patients. Serum MYCN protein levels were higher in patients with HCC, decreased after surgical resection of HCC, and were associated with liver functional reserve and fibrosis markers, as well as long-term HCC prognosis (>4 years). Subgroup analysis of a phase 3 clinical trial of ACR identified serum MYCN as the risk factor most strongly associated with HCC recurrence. Patients with HCC with higher serum MYCN levels after a 4-week treatment of ACR exhibited a significantly higher risk of recurrence (hazard ratio 3.27; p = .022). In conclusion, serum MYCN holds promise for biomarker-based precision medicine for the prevention of HCC, long-term prognosis of early-stage HCC, and identification of high-response subgroups for ACR-based treatment.
Subjects
MYCN; acyclic retinoid; biomarker; hepatocellular carcinoma; liquid biopsy
SDGs
Type
journal article