The Overexpression of CCAR1 in Hepatocellular Carcinoma Associates with Poor Prognosis.
OBJECTIVE
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.


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).


CONCLUSIONS
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.
Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Sang Yun
SY
Ha
Department of Molecular Biology, Samsung Advanced Institute for Health Science and Technology, Sungkyunkwan University School of Medicine, Seoul, Korea.
Jeong Hoon
JH
Kim
Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Jung Wook
JW
Yang
Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Jimin
J
Kim
Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Binnari
B
Kim
Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Cheol-Keun
CK
Park
D000293:Adolescent; D000328:Adult; D000368:Aged; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000401:mortality* / Q000473:pathology* / Q000601:surgery; D018797:Cell Cycle Proteins / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006498:Hepatectomy; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008099:Liver / Q000473:pathology; D008113:Liver Neoplasms / Q000097:blood / Q000401:mortality* / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000401:mortality* / Q000473:pathology*; D009367:Neoplasm Staging; D011379:Prognosis; D055815:Young Adult; D000509:alpha-Fetoproteins / Q000032:analysis
D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor; C477529:CCAR1 protein, human; D018797:Cell Cycle Proteins; D000509:alpha-Fetoproteins
CCAR1; Hepatocellular carcinoma; Prognosis