Clinical significance of CDT1 mRNA expression in chronic hepatitis C or liver cirrhosis

Masahiro Ogawa; Mitsuhiko Moriyama; Hitomi Nakamura; Toshikatu Shibata; Kazumichi Kuroda; Masahiko Sugitani

doi:10.3164/jcbn.23-54

Clinical significance of CDT1 mRNA expression in chronic hepatitis C or liver cirrhosis

J Clin Biochem Nutr. 2024 Mar;74(2):169-178. doi: 10.3164/jcbn.23-54. Epub 2023 Aug 11.

Authors

Masahiro Ogawa¹, Mitsuhiko Moriyama^{1

2}, Hitomi Nakamura¹, Toshikatu Shibata¹, Kazumichi Kuroda¹, Masahiko Sugitani³

Affiliations

¹ Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-Kamimachi, Itabashi-ku, Tokyo 173-8610, Japan.
² Sashiogi Recuperation Hospital, 1348-1 Hourai, Nishi-ku, Saitama city, Saitama 331-0074, Japan.
³ Department of Pathology, Nihon University School of Medicine, 30-1 Oyaguchi-Kamimachi, Itabashi-ku, Tokyo 173-8610, Japan.

Abstract

We have previously reported that chromatin licensing and DNA replication factor 1 (CDT1) is associated with the postoperative recurrence of hepatocellular carcinoma (HCC). Based on this fact, we verified whether CDT1 mRNA expression is also associated with HCC development from chronic hepatitis C (CHC) and liver cirrhosis (LC). There were 142 cases with CHC or LC who underwent liver biopsy. Detection of CDT1 mRNA in liver was performed by RT-qPCR using frozen liver biopsy tissues. We examined the association between the CDT1 mRNA expression and clinical conditions and long-term outcome. We then examined the association between serum cytokine/chemokine levels and CDT1 mRNA expression in 58 cases. The cumulative incidence rates of HCC development in cases with CDT1 mRNA in the low expression group showed significantly lower than those in the high expression group (p = 0.0391). A significant correlation was found between CDT1 mRNA expression and the extent of proliferation of atypical hepatocytes in hematoxylin and eosin-stained sections (p<0.0001). CDT1 mRNA expression has been associated with cytokines involved in tumorigenesis in experimental and human cancers. We found that cases with high CDT1 mRNA expression were at risk for developing HCC, even if they were CHC or LC.

Keywords: chromatin licensing and DNA replication factor (CDT1); chronic hepatitis C; hepatocellular carcinoma; proliferation of atypical hepatocytes; serum cytokines/chemokine concentration.