Abstract
Simple SummaryPoly (ADP-ribose) polymerases (PARPs) are DNA damage repair proteins that are involved in various biological activities ranges from cell proliferation to cell death. The prognostic significance of PARPs is not fully clarified in various cancers. This systematic review aims to reveal the prognostic value of PARP expression in solid cancers and to further correlate with clinicopathological and immunohistochemical markers. Lastly, the inhibition of this pathway through its specific inhibitors may increase the survival of patients with high PARP expression.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.
Highlights
(ADP-ribose) polymerases (PARPs) are DNA damage repair proteins, and their inhibitors have received great attention from researchers owing to their promising results 4.0/).in clinical trials [1,2]
The initial database searches identified a total of 5589 records (2373 in MEDLINE, 3113 in EMBASE, and 90 in the Cochrane library), and 13 supplementary records were identified from forward and backward searches, all of which were imported to Endnote
The present meta-analysis revealed that a higher expression of Poly (ADP-ribose) polymerase (PARP) could act as a risk factor for poor overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS) in various solid cancers, such as breast, ovary, lung, and liver cancers
Summary
(ADP-ribose) polymerases (PARPs) are DNA damage repair proteins, and their inhibitors have received great attention from researchers owing to their promising results 4.0/).in clinical trials [1,2]. (ADP-ribose) polymerases (PARPs) are DNA damage repair proteins, and their inhibitors have received great attention from researchers owing to their promising results 4.0/). Upon DNA damage, PARPs bind to the damaged site and produce a poly-ADP chain from the NAD+. The overexpression of PARPs has been examined in various cancers and is linked with a resistance to DNA-damaging therapeutic agents [2,3]. The blockade of this pathway by specific PARP inhibitors inhibits the recruitment of DNA repair proteins and causes cell death, which may extend the long-term survival of patients with cancer [2,4]. The efficacy of PARP inhibitors is currently being investigated in clinical trials. Olaparib is the first US Food and Drug Administration (FDA)-approved PARP inhibitor for use in treating advanced ovarian cancer with germline
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