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Serum MYCN as a predictive biomarker of prognosis and therapeutic response in the prevention of hepatocellular carcinoma recurrence.
- Source :
-
International journal of cancer [Int J Cancer] 2024 Aug 01; Vol. 155 (3), pp. 582-594. Date of Electronic Publication: 2024 Feb 21. - Publication Year :
- 2024
-
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.<br /> (© 2024 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)
- Subjects :
- Adult
Aged
Female
Humans
Male
Middle Aged
Prognosis
Biomarkers, Tumor blood
Biomarkers, Tumor genetics
Carcinoma, Hepatocellular blood
Carcinoma, Hepatocellular pathology
Carcinoma, Hepatocellular genetics
Carcinoma, Hepatocellular drug therapy
Liver Neoplasms blood
Liver Neoplasms genetics
Liver Neoplasms drug therapy
Liver Neoplasms prevention & control
Liver Neoplasms pathology
N-Myc Proto-Oncogene Protein genetics
Neoplasm Recurrence, Local prevention & control
Neoplasm Recurrence, Local blood
Proto-Oncogene Mas
Subjects
Details
- Language :
- English
- ISSN :
- 1097-0215
- Volume :
- 155
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- International journal of cancer
- Publication Type :
- Academic Journal
- Accession number :
- 38380807
- Full Text :
- https://doi.org/10.1002/ijc.34893