1. Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea.
2. Department of Pathology, Chung-Ang University College of Medicine, Seoul, Korea.
3. Department of Pathology, National Medical Center, Seoul, Korea.
4. College of Pharmacy, Chung-Ang University, Seoul, Korea.
5. Department of Surgery, Chung-Ang University College of Medicine, Seoul, Korea.
Purpose: This study aimed to investigate the relationship between DNA damage response (DDR) related protein expression and clinical outcomes of patients with stage II and III gastric cancer undergoing gastrectomy.
Materials and Methods: From January 2005 to December 2017, 217 gastrectomized patients with stage II and III gastric cancer were analyzed for disease-free and overall survival (DFS and OS, respectively) based on their DDR expression status. We performed the immunohistochemical assessment of MLH1, MSH2, at-rich interaction domain 1 (ARID1A), poly adenosine diphosphate-ribose polymerase 1 (PARP-1), breast cancer susceptibility gene 1 (BRCA1), and ataxia-telangiectasia mutated (ATM) using formalin-fixed paraffin-embedded (FFPE) samples.
Results: Among the 217 patients studied, the most common DDR gene whose expression was suppressed was high PARP-1 (n = 120, 55.3%), followed by ATM (n = 62, 28.6%), ARID1A (n = 45, 20.7%), MLH1 (n = 33, 15.2%), BRCA1 (n = 25, 11.5%), and MSH2 (n = 9, 4.1%). The low-expression PARP-1 group exhibited a significantly shorter 5-year OS rate than the high-expression PARP-1 group (48.1% vs. 62.7%; HR 1.519, 95% CI = 1.011-2.283, P = 0.044). In the multivariate OS analysis, TNM stage (II vs. III) (HR = 5.172, P < 0.001), low PARP-1 expression (HR = 1.697, P = 0.013) and adjuvant chemotherapy (HR = 0.382, P < 0.001) were the only significant prognostic factors.
Conclusions: Low PARP-1 expression level could be an indicator of poor prognosis in gastrectomized patients with stage II and III gastric cancer.
Keywords: DNA damage response (DDR), Poly adenosine diphosphate-ribose polymerase 1 (PARP-1), Gastric cancer, Survival, Gastrectomy