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Updated: Jun 18, 2026

Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
Loss of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) expression in gastric cancers
Hye Seung Lee1, Han-Kwang Yang, Woo Ho Kim
1Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
Purpose:
DNA-PKcs is one of the DNA repair genes. It was recently found that hyperplasia and dysplasia of the intestinal mucosa and the production of aberrant crypt foci were developed in DNA-PKcs-null mice, and this suggests a suppressive role for DNA-PKcs in tumorigenesis.
Materials And Methods:
To investigate the possible relationship between the clinico-pathologic characteristics and the survival of gastric cancer patients, the expression status of DNA-PKcs was determined in 279 consecutive gastric cancers. Immunohistochemical analysis was performed to evaluate the expression levels of DNA-PKcs protein by using the tissue array method.
Results:
Out of 279 consecutive gastric cancers, 63 cases (22.6%) showed the loss of DNA-PKcs expression. The loss of DNA-PKcs expression was significantly associated with advanced cancer (p<0.001), lymphatic invasion (p=0.001), lymph node metastasis (p=0.009), and advanced pTNM stage (p=0.009). Univariate survival analysis revealed that patients with the loss of DNA-PKcs expression had significantly poorer survival than those patients with intact DNA-PKcs expression (p=0.004). Moreover, the loss of DNA-PKcs expression was identified to correlate with a lower survival in the subgroup of stage I gastric cancer patients (p=0.037).
Conclusion:
The loss of DNA-PKcs expression was found in 23% of human gastric cancers and this was identified to significantly correlate with poor patient survival, especially for stage I gastric cancer patients.
Insights
Loss of DNA-PKcs expression in gastric cancer correlates with advanced disease and poorer survival, particularly in early stages. This DNA repair gene
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- DNA-PKcs (DNA-dependent protein kinase catalytic subunit) is a key DNA repair protein.
- Previous studies in mice suggest DNA-PKcs has a tumor-suppressive role in intestinal tumorigenesis.
- Understanding DNA-PKcs expression in human cancers is crucial for prognostic insights.
Purpose of the Study:
- To investigate the association between DNA-PKcs expression and clinicopathological characteristics in gastric cancer.
- To determine if DNA-PKcs expression status impacts patient survival in gastric cancer.
- To explore the prognostic significance of DNA-PKcs loss in different stages of gastric cancer.
Main Methods:
- Immunohistochemical analysis of DNA-PKcs protein expression was performed on 279 gastric cancer tissue samples using tissue arrays.
- Clinicopathological data, including cancer stage, lymphatic invasion, and lymph node metastasis, were collected.
- Statistical analyses, including univariate survival analysis, were used to evaluate correlations.
Main Results:
- Loss of DNA-PKcs expression was observed in 22.6% (63/279) of gastric cancers.
- DNA-PKcs loss significantly correlated with advanced cancer stage, lymphatic invasion, lymph node metastasis, and advanced pTNM stage.
- Patients with lost DNA-PKcs expression exhibited significantly poorer survival (p=0.004), notably in Stage I gastric cancer (p=0.037).
Conclusions:
- The loss of DNA-PKcs expression is a frequent event in human gastric cancer (23%).
- Loss of DNA-PKcs expression is a significant independent predictor of poor patient survival.
- This finding is particularly relevant for Stage I gastric cancer, highlighting DNA-PKcs as a potential prognostic biomarker.
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