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.

Abstract

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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