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Serum MYCN as a predictive biomarker of prognosis and therapeutic response in the prevention of hepatocellular carcinoma recurrence
International Journal of Cancer ( IF 6.4 ) Pub Date : 2024-02-21 , DOI: 10.1002/ijc.34893 Xian‐Yang Qin, Yohei Shirakami, Masao Honda, Shiou‐Hwei Yeh, Kazushi Numata, Ya‐Yun Lai, Chiao‐Ling Li, Feifei Wei, Yali Xu, Kenji Imai, Koji Takai, Makoto Chuma, Nagisa Komatsu, Yutaka Furutani, Luc Gailhouste, Hiroshi Aikata, Kazuaki Chayama, Masaru Enomoto, Ryosuke Tateishi, Kazunori Kawaguchi, Tatsuya Yamashita, Shuichi Kaneko, Katsuya Nagaoka, Motohiko Tanaka, Yutaka Sasaki, Yasuhito Tanaka, Hideo Baba, Kouichi Miura, Sae Ochi, Takahiro Masaki, Soichi Kojima, Tomokazu Matsuura, Masahito Shimizu, Pei‐Jer Chen, Hisataka Moriwaki, Harukazu Suzuki
International Journal of Cancer ( IF 6.4 ) Pub Date : 2024-02-21 , DOI: 10.1002/ijc.34893 Xian‐Yang Qin, Yohei Shirakami, Masao Honda, Shiou‐Hwei Yeh, Kazushi Numata, Ya‐Yun Lai, Chiao‐Ling Li, Feifei Wei, Yali Xu, Kenji Imai, Koji Takai, Makoto Chuma, Nagisa Komatsu, Yutaka Furutani, Luc Gailhouste, Hiroshi Aikata, Kazuaki Chayama, Masaru Enomoto, Ryosuke Tateishi, Kazunori Kawaguchi, Tatsuya Yamashita, Shuichi Kaneko, Katsuya Nagaoka, Motohiko Tanaka, Yutaka Sasaki, Yasuhito Tanaka, Hideo Baba, Kouichi Miura, Sae Ochi, Takahiro Masaki, Soichi Kojima, Tomokazu Matsuura, Masahito Shimizu, Pei‐Jer Chen, Hisataka Moriwaki, Harukazu Suzuki
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.
更新日期：2024-02-21
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