DNA damage response-related proteins in gastric cancer: ATM, Chk2 and p53 expression and their prognostic value.

Abstract

OBJECTIVES:

The aims of this study were to assess expressions of the DNA damage response (DDR)-related proteins and to investigate their clinical significances in gastric carcinoma.

METHODS:

Two independent cohorts, a training set (n=524) and validation set (n=394), of gastric cancer patients were enrolled. Ataxia telangiectasia mutated (ATM), checkpoint kinase 2 (Chk2), and p53 expressions were examined by immunohistochemistry using tissue microarray.

RESULTS:

ATM loss, Chk2 loss, and p53 positivity were observed in 21.8, 14.1, and 36.1% of the training set, and in 17.3, 12.2, and 35.8% of the validation set, respectively. In the training set, the aberrant expressions of ATM, Chk2, or p53 were significantly associated with an advanced TNM stage and poor disease-specific survival. This association was verified in the validation set. Chk2 positivity and p53 negativity were significantly related to a prolonged disease-specific survival. Also, patients with nonaberrant expressional levels of all 3 DDR-related proteins had a more favorable outcome than others. Multivariate analyses showed that Chk2 loss and at least 1 aberrant DDR-related protein remained as independent prognostic factors of poor disease-specific survival.

CONCLUSIONS:

This study elucidated the prognostic implications of DDR-related proteins, and suggests that their aberrant expressions play critical roles in the development and progression of gastric cancer.

• Authors: Hee Eun Lee, Nayoung Han, Min A Kim, Hye Seung Lee, Han-Kwang Yang, Byung Lan Lee, Woo Ho Kim
• Journal: Pathobiology : journal of immunopathology, molecular and cellular biology (Pathobiology) Vol. 81 Issue 1 Pg. 25-35 ( 2014) ISSN: 1423-0291 [Electronic] Switzerland
• PMID: 23969480 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 S. Karger AG, Basel.

Chemical References

• Biomarkers, Tumor
• TP53 protein, human
• Tumor Suppressor Protein p53
• Checkpoint Kinase 2
• ATM protein, human
• Ataxia Telangiectasia Mutated Proteins
• CHEK2 protein, human

Topics

• Adenocarcinoma (metabolism, mortality, pathology)
• Adult
• Aged
• Ataxia Telangiectasia Mutated Proteins (analysis, biosynthesis)
• Biomarkers, Tumor (analysis)
• Checkpoint Kinase 2 (analysis, biosynthesis)
• DNA Damage
• Female
• Humans
• Immunohistochemistry
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Neoplasm Staging
• Prognosis
• Proportional Hazards Models
• Stomach Neoplasms (metabolism, mortality, pathology)
• Tissue Array Analysis
• Tumor Suppressor Protein p53 (analysis, biosynthesis)