Peretinoin, an acyclic retinoid, improves the hepatic gene signature of chronic hepatitis C following curative therapy of hepatocellular carcinoma.

Abstract

BACKGROUND:

The acyclic retinoid, peretinoin, has been shown to be effective for suppressing hepatocellular carcinoma (HCC) recurrence after definitive treatment in a small-scale randomized clinical trial. However, little has been documented about the mechanism by which peretinoin exerts its inhibitory effects against recurrent HCC in humans in vivo.

METHODS:

Twelve hepatitis C virus-positive patients whose HCC had been eradicated through curative resection or ablation underwent liver biopsy at baseline and week 8 of treatment with either a daily dose of 300 or 600 mg peretinoin. RNA isolated from biopsy samples was subjected to gene expression profile analysis.

RESULTS:

Peretinoin treatment elevated the expression levels of IGFBP6, RBP1, PRB4, CEBPA, G0S2, TGM2, GPRC5A, CYP26B1, and many other retinoid target genes. Elevated expression was also observed for interferon-, Wnt-, and tumor suppressor-related genes. By contrast, decreased expression levels were found for mTOR- and tumor progression-related genes. Interestingly, gene expression profiles for week 8 of peretinoin treatment could be classified into two groups of recurrence and non-recurrence with a prediction accuracy rate of 79.6% (P<0.05). In the liver of patients with non-recurrence, expression of PDGFC and other angiogenesis genes, cancer stem cell marker genes, and genes related to tumor progression was down-regulated, while expression of genes related to hepatocyte differentiation, tumor suppression genes, and other genes related to apoptosis induction was up-regulated.

CONCLUSIONS:

Gene expression profiling at week 8 of peretinoin treatment could successfully predict HCC recurrence within 2 years. This study is the first to show the effect of peretinoin in suppressing HCC recurrence in vivo based on gene expression profiles and provides a molecular basis for understanding the efficacy of peretinoin.

• Authors: Masao Honda, Taro Yamashita, Tatsuya Yamashita, Kuniaki Arai, Yoshio Sakai, Akito Sakai, Mikiko Nakamura, Eishiro Mizukoshi, Shuichi Kaneko
• Journal: BMC cancer (BMC Cancer) Vol. 13 Pg. 191 (Apr 15 2013) ISSN: 1471-2407 [Electronic] England
• PMID: 23587162 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Retinoids
• (2E,4E,6E,10E)-3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid

Topics

• Aged
• Analysis of Variance
• Antineoplastic Agents (pharmacology, therapeutic use)
• Carcinoma, Hepatocellular (complications, drug therapy, genetics, surgery)
• Female
• Gene Expression (drug effects)
• Gene Expression Profiling
• Hepatitis C, Chronic (complications)
• Humans
• Liver Neoplasms (complications, drug therapy, genetics, surgery)
• Male
• Middle Aged
• Neoplasm Recurrence, Local (genetics, prevention & control)
• Oligonucleotide Array Sequence Analysis
• Retinoids (pharmacology, therapeutic use)