High Poly(ADP-Ribose) Polymerase Expression Does Relate to Poor Survival in Solid Cancers: A Systematic Review and Meta-Analysis

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 revea...

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Autores principales:	Nishant Thakur, Kwangil Yim, Jamshid Abdul-Ghafar, Kyung Jin Seo, Yosep Chong
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	poly(ADP-ribose) polymerases neoplasm BRCA1 and BRCA2 prognosis meta-analysis Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/ebee618a9b5a4398b4aef6553bb27b11
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spelling	oai:doaj.org-article:ebee618a9b5a4398b4aef6553bb27b112021-11-25T17:00:59ZHigh Poly(ADP-Ribose) Polymerase Expression Does Relate to Poor Survival in Solid Cancers: A Systematic Review and Meta-Analysis10.3390/cancers132255942072-6694https://doaj.org/article/ebee618a9b5a4398b4aef6553bb27b112021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/22/5594https://doaj.org/toc/2072-6694Poly (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, <i>p</i> < 0.001), disease-free survival (DFS) (HR = 1.15, 95% CI = 1.10–1.21, <i>p</i> < 0.001), and progression-free survival (PFS) (HR = 1.05, 95% CI = 1.03–1.08, <i>p</i> < 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, <i>p</i> < 0.001), ovary cancers (HR = 1.21, 95% CI = 1.10–1.33, <i>p</i> = 0.001), lung cancers (HR = 2.11, 95% CI = 1.29–3.45, <i>p</i> = 0.003), and liver cancers (HR = 3.29, 95% CI = 1.94–5.58, <i>p</i> < 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.Nishant ThakurKwangil YimJamshid Abdul-GhafarKyung Jin SeoYosep ChongMDPI AGarticlepoly(ADP-ribose) polymerasesneoplasmBRCA1 and BRCA2prognosismeta-analysisNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5594, p 5594 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	poly(ADP-ribose) polymerases neoplasm BRCA1 and BRCA2 prognosis meta-analysis Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	poly(ADP-ribose) polymerases neoplasm BRCA1 and BRCA2 prognosis meta-analysis Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Nishant Thakur Kwangil Yim Jamshid Abdul-Ghafar Kyung Jin Seo Yosep Chong High Poly(ADP-Ribose) Polymerase Expression Does Relate to Poor Survival in Solid Cancers: A Systematic Review and Meta-Analysis
description	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, <i>p</i> < 0.001), disease-free survival (DFS) (HR = 1.15, 95% CI = 1.10–1.21, <i>p</i> < 0.001), and progression-free survival (PFS) (HR = 1.05, 95% CI = 1.03–1.08, <i>p</i> < 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, <i>p</i> < 0.001), ovary cancers (HR = 1.21, 95% CI = 1.10–1.33, <i>p</i> = 0.001), lung cancers (HR = 2.11, 95% CI = 1.29–3.45, <i>p</i> = 0.003), and liver cancers (HR = 3.29, 95% CI = 1.94–5.58, <i>p</i> < 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.
format	article
author	Nishant Thakur Kwangil Yim Jamshid Abdul-Ghafar Kyung Jin Seo Yosep Chong
author_facet	Nishant Thakur Kwangil Yim Jamshid Abdul-Ghafar Kyung Jin Seo Yosep Chong
author_sort	Nishant Thakur
title	High Poly(ADP-Ribose) Polymerase Expression Does Relate to Poor Survival in Solid Cancers: A Systematic Review and Meta-Analysis
title_short	High Poly(ADP-Ribose) Polymerase Expression Does Relate to Poor Survival in Solid Cancers: A Systematic Review and Meta-Analysis
title_full	High Poly(ADP-Ribose) Polymerase Expression Does Relate to Poor Survival in Solid Cancers: A Systematic Review and Meta-Analysis
title_fullStr	High Poly(ADP-Ribose) Polymerase Expression Does Relate to Poor Survival in Solid Cancers: A Systematic Review and Meta-Analysis
title_full_unstemmed	High Poly(ADP-Ribose) Polymerase Expression Does Relate to Poor Survival in Solid Cancers: A Systematic Review and Meta-Analysis
title_sort	high poly(adp-ribose) polymerase expression does relate to poor survival in solid cancers: a systematic review and meta-analysis
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/ebee618a9b5a4398b4aef6553bb27b11
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High Poly(ADP-Ribose) Polymerase Expression Does Relate to Poor Survival in Solid Cancers: A Systematic Review and Meta-Analysis

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