Are DNA repair factors promising biomarkers for personalized therapy in gastric cancer?

Abstract

Chronic inflammation is a driving force for gastric carcinogenesis. Reactive oxygen species (ROS) generated during the inflammatory process generates DNA damage that is processed through the DNA repair pathways. In this study, we profiled key DNA repair proteins (single-strand-selective monofunctional uracil-DNA glycosylase 1 [SMUG1], Flap endonuclease 1 [FEN1], X-ray repair cross-complementing gene 1 [XRCC1], and Ataxia telangiectasia mutated [ATM]) involved in ROS-induced oxidative DNA damage repair in gastric cancer and correlated to clinicopathological outcomes. High expression of SMUG1, FEN1, and XRCC1 correlated to high T-stage (T3/T4) (p-values: 0.001, 0.005, and 0.02, respectively). High expression of XRCC1 and FEN1 also correlated to lymph node-positive disease (p-values: 0.009 and 0.02, respectively). High expression of XRCC1, FEN1, and SMUG1 correlated with poor disease-specific survival (DSS) (p-values: 0.001, 0.006, and 0.05, respectively) and poor disease-free survival (DFS) (p-values: 0.001, 0.001, and 0.02, respectively). Low expression of ATM correlated to lymph node positivity (p=0.03), vascular invasion (p=0.05), and perineural invasion (p=0.005) and poor DFS (p=0.001) and poor DSS (p=0.003). In the multivariate Cox model, high XRCC1 and low ATM were independently associated with poor survival (p=0.008 and 0.011, respectively). Our observation supports the hypothesis that DNA repair factors are promising biomarkers for personalized therapy in gastric cancer.

• Authors: Tarek Abdel-Fatah, Arvind Arora, Ipek Gorguc, Rachel Abbotts, Sarah Beebeejaun, Sarah Storr, Vivek Mohan, Claire Hawkes, Irshad Soomro, Dileep N Lobo, Simon L Parsons, Srinivasan Madhusudan
• Journal: Antioxidants & redox signaling (Antioxid Redox Signal) Vol. 18 Issue 18 Pg. 2392-8 (Jun 20 2013) ISSN: 1557-7716 [Electronic] United States
• PMID: 22894650 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• DNA-Binding Proteins
• Reactive Oxygen Species
• X-ray Repair Cross Complementing Protein 1
• XRCC1 protein, human
• ATM protein, human
• Ataxia Telangiectasia Mutated Proteins
• Flap Endonucleases
• FEN1 protein, human
• SMUG1 protein, human
• Uracil-DNA Glycosidase

Topics

• Adenocarcinoma (metabolism, pathology, secondary, therapy)
• Aged
• Ataxia Telangiectasia Mutated Proteins (metabolism)
• Biomarkers, Tumor (metabolism)
• DNA Repair
• DNA-Binding Proteins (metabolism)
• Female
• Flap Endonucleases (metabolism)
• Humans
• Kaplan-Meier Estimate
• Lymphatic Metastasis
• Male
• Multivariate Analysis
• Precision Medicine
• Proportional Hazards Models
• Reactive Oxygen Species
• Stomach Neoplasms (metabolism, mortality, pathology, therapy)
• Uracil-DNA Glycosidase (metabolism)
• X-ray Repair Cross Complementing Protein 1