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High Poly(ADP-Ribose) Polymerase Expression Does Relate to Poor Survival in Solid Cancers: A Systematic Review and
Nishant Thakur1, Kwangil Yim1, Jamshid Abdul-Ghafar1
1Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul 07345, Korea.
Abstract:
Poly (ADP-ribose) polymerase (PARP) is a DNA damage repair protein, and its inhibitors have shown promising results in clinical trials. The prognostic significance of PARP is inconsistent in studies of various cancers. In the present study, we conducted a systematic review and meta-analysis to reveal the prognostic and clinicopathological significance of PARP expression in multiple solid cancers. We searched the MEDLINE, EMBASE, and Cochrane databases for relevant research articles published from 2005 to 2021. The pooled hazard ratio (HR) with confidence interval (CI) was calculated to investigate the relationship between PARP expression and survival in multiple solid cancers. In total, 10,667 patients from 31 studies were included. A significant association was found between higher PARP expression and overall survival (OS) (HR = 1.54, 95% CI = 1.34-1.76, p < 0.001), disease-free survival (DFS) (HR = 1.15, 95% CI = 1.10-1.21, p < 0.001), and progression-free survival (PFS) (HR = 1.05, 95% CI = 1.03-1.08, p < 0.001). Subgroup analyses showed that PARP overexpression was significantly related to poor OS in patients with breast cancers (HR = 1.38, 95% CI = 1.28-1.49, p < 0.001), ovary cancers (HR = 1.21, 95% CI = 1.10-1.33, p = 0.001), lung cancers (HR = 2.11, 95% CI = 1.29-3.45, p = 0.003), and liver cancers (HR = 3.29, 95% CI = 1.94-5.58, p < 0.001). Regarding ethnicity, Asian people have almost twice their worst survival rate compared to Caucasians. The pooled odds ratio analysis showed a significant relationship between higher PARP expression and larger tumour size, poor tumour differentiation, lymph node metastasis, distant metastasis, higher TNM stage and lymphovascular invasion, and positive immunoreactivity for Ki-67, BRCA1, and BRCA2. In addition, nuclear expression assessed by the QS system using Abcam and Santa Cruz Biotechnology seems to be the most commonly used and reproducible IHC method for assessing PARP expression. This meta-analysis revealed that higher PARP expression was associated with a worse OS, DFS, and PFS in patients with solid cancers. Moreover, inhibition of this pathway through its specific inhibitors may extend the survival of patients with higher PARP expression.
