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

ABSTRACT: 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, ?-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.In 167 HCC patients with long-term follow-up, CCAR1 protein expression was examined by immunohistochemistry.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 ?-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 ?-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).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 ?-fetoprotein levels or early stage HCC.

SUBMITTER: Ha SY

PROVIDER: S-EPMC4946359 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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

Ha Sang Yun SY Kim Jeong Hoon JH Yang Jung Wook JW Kim Jimin J Kim Binnari B Park Cheol-Keun CK

Cancer research and treatment 20151016 3

<h4>Purpose</h4>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.<h4>Materials and methods</h4>In 167 HCC patients w ...[more]

PMID: 26511806

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Project description:Objectives: DNA damage inducible transcript 4 (DDIT4) plays a key role in different cancers, but the role of DDIT4 in lung adenocarcinoma (LUAD) is not completely understood. The aim of this study was to evaluate the utility of DDIT4 as a prognostic biomarker for LUAD. Methods: First, DDIT4 mRNA expression in LUAD cell lines (A549, H1299 and HBE) and tissues (89 cases) was assessed by RT-PCR. Next, DDIT4 protein expression in LUAD tissues and normal tissues was assessed by immunohistochemistry (75 cases). Then, the correlation between DDIT4 expression and overall survival was analyzed using the Kaplan-Meier method. After that, we verified the utility of the DDIT4 gene as a prognostic marker of lung cancer in the TCGA database (1133 cases). Finally, the possible mechanism of the DDIT4 gene as a prognostic marker of LUAD was preliminarily explored. Results: mRNA levels of DDIT4 in HBE cells were significantly lower than in A549 and H1299 cells (P<0.05), and expression of the DDIT4 gene in cancer tissues was significantly higher than in adjacent tissues (P<0.0001). Immunohistochemical staining results showed that high expression of DDIT4 accounted for approximately 68.0% of LUAD tissues. DDIT4 expression was significantly correlated with differentiation (P < 0.05). However, it was not correlated with sex, age, smoking, tumor size, lymph node metastasis, or TNM stage (P>0.05). The survival analysis demonstrated that high DDIT4 expression was correlated with shorter overall survival (P < 0.05). Univariate and multivariate analyses indicated that DDIT4 was an independent predictor of overall survival for LUAD, which was confirmed by data from the TCGA database. Finally, we found that DDIT4 gene expression was significantly increased in the hypoxic environment compared to the normal oxygen environment, indicating that the DDIT4 gene may play an important role in the hypoxic microenvironment of tumor tissue. Conclusion: High expression levels of DDIT4 correlated with poor overall survival in patients with LUAD, and DDIT4 was an independent predictor of overall survival. These findings provide new insight for understanding the development of LUAD.

Dataset Information

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

Publications

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

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