Low PARP-1 expression level is an indicator of poor prognosis in patients with stage II and III gastric cancer

Abstract

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.

Predictive and Prognostic Biomarkers and Tumor Antigens for Targeted Therapy in Urothelial Carcinoma

“…Patients who underwent surgery and whose tumors showed low expression of PARP-1 exhibited a shorter overall survival than that of those with high expression. This retrospective study suggested that PARP-1 expression could be of prognostic value in select solid tumor models [73]. Other studies of PARP expression in locally advanced breast cancer and pancreatic cancer also reported that low expression of PARP-1 was associated with poor prognosis [74,75].…”

MiRNA polymorphisms affect the prognosis of gastric cancer: insights from Xianyou, Fujian

“…Elevated expression levels of miR-203, miR-218, and miR-194 have been correlated with a favorable prognosis for gastric cancer, while diminished expression of miR-17-5p and miR-34a serves as a marker for an unfavorable prognosis ( 6 , 20 , 21 ). Furthermore, a diminished expression of PARP-1, a DNA damage response (DDR)-associated protein, has been identified as a prognostic indicator for patients with stage 2 and 3 gastric cancer ( 22 ). Given its role as a DDR-associated gene, the low expression of MSH2 may similarly contribute to an unfavorable prognosis.…”

Transcriptomic Analysis of CRISPR/Cas9-Mediated PARP1-Knockout Cells under the Influence of Topotecan and TDP1 Inhibitor

“…PARP1 inhibition was found to be effective in the treatment of tumors carrying mutations in BRCA1/2 genes exploiting the concept of synthetic lethality [ 85 ]. PARP1 is mostly over-expressed in cancers [ 86 ], but in the work [ 87 ] low PARP1 expression level was found in the clinical samples from the patients with gastric cancer. The inhibition of PARP1 activity could sensitize tumor cells to the action of chemotherapeutic drugs.…”