Cancer Res Treat.  2016 Jul;48(3):1065-1073. 10.4143/crt.2015.302.

The Overexpression of CCAR1 in Hepatocellular Carcinoma Associates with Poor Prognosis

Affiliations
  • 1Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. ckpark@skku.edu
  • 2Department of Molecular Biology, Samsung Advanced Institute for Health Science and Technology, Sungkyunkwan University School of Medicine, Seoul, Korea.

Abstract

PURPOSE
Cell division cycle and apoptosis regulator 1 (CCAR1) plays a dynamic role in regulation of cell growth and apoptosis by serving as a cofactor of steroid/thyroid nuclear receptors, β-catenin, and p53 in a variety of cell types including different cancer cells. However, whether CCAR1 protein is overexpressed in hepatocellular carcinoma (HCC) and the prognostic significance of CCAR1 protein expression in HCC have not been reported.
MATERIALS AND METHODS
In 167 HCC patients with long-term follow-up, CCAR1 protein expression was examined by immunohistochemistry.
RESULTS
High CCAR1 protein expression was observed in 149 of the 167 HCC cases (89.2%) and showed significant correlation with microvascular invasion, intrahepatic metastasis, higher American Joint Committee on Cancer (AJCC) T stage, and early recurrence. High CCAR1 expression showed an unfavorable effect on recurrence-free survival (RFS) (p=0.002). In subgroup analysis, among patients with α-fetoprotein ≤ 20 ng/mL (n=54) and patients with AJCC T stage 1 (n=62), significant differences in RFS were observed between high CCAR1 expression groups and low CCAR1 expression groups (p=0.015 and p=0.004, respectively). High CCAR1 expression tended to be an independent predictor of shorter RFS (p=0.054) and showed an unfavorable effect on overall survival (OS) (p=0.015). In subgroup analysis, among patients with α-fetoprotein ≤ 20 ng/mL (n=54), significant difference in OS was observed between high CCAR1 expression group and low CCAR1 expression group (p=0.046).
CONCLUSION
CCAR1 protein could be a potential biomarker predicting RFS in HCC patients after curative hepatectomy. In addition, CCAR1 had prognostic values in HCC patients with normal serum α-fetoprotein levels or early stage HCC.

Keyword

CCAR1; Hepatocellular carcinoma; Prognosis

MeSH Terms

Apoptosis
Carcinoma, Hepatocellular*
Cell Cycle
Follow-Up Studies
Hepatectomy
Humans
Immunohistochemistry
Joints
Neoplasm Metastasis
Prognosis*
Receptors, Cytoplasmic and Nuclear
Recurrence
Receptors, Cytoplasmic and Nuclear

Figure

  • Fig. 1. Immunostaining of cell division cycle and apoptosis regulator 1 in hepatocellular carcinoma shows high nuclear immunoreactivity (horseradish peroxidase stain, ×200).

  • Fig. 2. Kaplan-Meier survival curves showing recurrence-free survival among all patients (A), patients with α-fetoprotein (AFP) ≤ 20 ng/mL (B), patients with American Joint Committee on Cancer (AJCC) T stage 1 (C), and patients with tumor size ≤ 5.0 cm (D) according to the cell division cycle and apoptosis regulator 1 expression.

  • Fig. 3. Kaplan-Meier survival curves showing overall survival among all patients (A), patients with α-fetoprotein (AFP) ≤ 20 ng/mL (B), patients with American Joint Committee on Cancer (AJCC) T stage 1 (C), and patients with tumor size ≤ 5.0 cm (D) according to the cell division cycle and apoptosis regulator 1 expression.


Reference

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