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01-03-2016 | Original Article

Overexpression of CDT1 Is a Predictor of Poor Survival in Patients with Hepatocellular Carcinoma

Authors: Dimitrios Karavias, Ioannis Maroulis, Helen Papadaki, Charalambos Gogos, Stavros Kakkos, Dionissios Karavias, Vasiliki Bravou

Published in: Journal of Gastrointestinal Surgery | Issue 3/2016

Abstract

Background

Genomic instability is a common feature in hepatocellular carcinoma. Deregulation of replication licensing factors has been shown to trigger DNA damage response contributing to genomic instability. Overexpression of DNA replication licensing factors chromatin licensing and DNA replication factor 1 (CDT1) and minichromosome maintenance complex component 7 (MCM7) has been previously reported in several human cancers. The aim of the present study was to evaluate the expression and prognostic significance of CDT1 and MCM7 in association with DNA damage response markers and p53 in patients with hepatocellular carcinoma.

Methods

Expression of CDT1, MCM7, p-H2A histone family member X (H2AX), phospho-ataxia telangiectasia-mutated (ATM)/ataxia telangiectasia rad3-related (ATR) substrate, and p53 was evaluated by immunohistochemistry on formalin-fixed paraffin-embedded surgical specimens from 111 patients who underwent hepatectomy for hepatocellular carcinoma. Statistical analysis was performed to evaluate associations between the studied proteins, clinicopathological parameters, and patient survival.

Results

CDT1 expression correlated with p-H2AX (p = 0.038), while MCM7 correlated with p-H2AX and phospho-ATM/ATR substrate (p < 0.001). Increased CDT1 expression was associated with higher tumor grade (p = 0.006) and tumor-node-metastasis (TNM) stage (p = 0.033). High CDT1 expression correlated significantly with reduced overall survival (60.8 and 26.5 % vs 82.8 and 53.0 %, for low CDT1 expression, at 2 and 5 years, respectively, p = 0.012) and was identified by multivariate analysis as an independent predictor of poor overall survival (p = 0.049).

Conclusions

Overexpression of CDT1 and MCM7 in hepatocellular carcinoma correlates with DNA damage response, and CDT1 overexpression is a significant prognostic biomarker in hepatocellular carcinoma.

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Title: Overexpression of CDT1 Is a Predictor of Poor Survival in Patients with Hepatocellular Carcinoma
Authors: Dimitrios Karavias
Ioannis Maroulis
Helen Papadaki
Charalambos Gogos
Stavros Kakkos
Dionissios Karavias
Vasiliki Bravou
Publication date: 01-03-2016
Publisher: Springer US
Published in: Journal of Gastrointestinal Surgery / Issue 3/2016
Print ISSN: 1091-255X
Electronic ISSN: 1873-4626
DOI: https://doi.org/10.1007/s11605-015-2960-7

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Overexpression of CDT1 Is a Predictor of Poor Survival in Patients with Hepatocellular Carcinoma

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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