High Poly(ADP-Ribose) Polymerase Expression Does Relate to Poor Survival in Solid Cancers: A Systematic Review and Meta-Analysis
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Search Strategy
2.2. Inclusion and Exclusion Criteria
2.3. Data Extraction and Quality Assessment
2.4. Statistical Methods
3. Results
3.1. Search Results
3.2. Study Characteristics
3.3. Association between PARP Expression and OS
3.4. Association of High PARP Expression with DFS and PFS
3.5. Association of High PARP Expression with Clinicopathological Parameters and Immunohistochemical Markers
3.6. Publication Bias
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Organ | Authors | Year | Country | Ethnicity | Study Period | Cancer Type/TNM Stage | Patients No. | Average Age (Range) | Median f/u (Years) | PARP Phenotype | Chemo Regimen | Detection Method | Hazard Ratio (CI 95%) | NOS Score |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Breast | Gonclaves [10] | 2011 | France | Caucasian | NA | IDC/ILC/MC/ others Stage I-IIIB | 2485 | NA | 8 | PARP-1 | Adj. Ant/Tax/CMF | PCR | OS: 1.16 (1.04–1.29) | 8 |
Minckwitz [16] | 2011 | Germany | Caucasian | 2001–2005 | IDC/ILC/ others Stage IIA-IIIB | 638 | NA | 4.8 | PARP | Neoadj. Ant/Tax | IHC | OS: 1.76 (0.87–3.50) DFS: 1.44 (1.88–2.36) | 8 | |
Rojo [17] | 2012 | Spain | Caucasian | 1998–2000 | IDC/ILC/ others NA | 330 | 58 (26–90) | 8.5 | PARP-1 | Adj. CMF/horm | IHC | OS: 1.82 (1.32–2.52) DFS: 10.05(5.42–18.66) | 8 | |
Donizy [9] | 2014 | Poland | Caucasian | 1993–1994 | IDC Stage IIA-IIB | 83 | 55.2 | 15 | PARP-1 | Neoadj. CMF/Ant | IHC | OS: 2.81 (1.12–7.03) | 7 | |
Aiad (1) * [7] | 2015 | Egypt | Caucasian | 2008–2012 | IDC Stage IIIB | 84 | 53 (29–86) | NA | PARP-1 | Neoadj.FEC | IHC | OS: 0.40 (0.08–2.05) | 7 | |
Aiad (2) * [7] | 2015 | Egypt | Caucasian | 2008–2012 | IDC Stage IIIB | 84 | 53 (29–86) | NA | PARP-1 | Neoadj.FEC | IHC | OS: 0.21 (0.04–1.00) | 7 | |
Green [11] | 2015 | UK | Caucasian | 1989–2004 | OBC Stage I–III | 1269 | 55 | NA | PARP-1 | NA | IHC | DFS: 1.32 (0.99–1.77) | 7 | |
Park [14] | 2015 | South Korea | Asian | 1997–2003 | IC/ILC Stage I–IV | 192 | 47 (22–73) | 11.2 | PARP-1 | Adj. Ant/Tax/CMF | IHC | OS: 3.64 (1.88–7.05) DFS: 1.95 (1.44–3.34) | 8 | |
Zhai [15] | 2015 | China | Asian | 2007–2012 | IDC/ILC Stage I-IIB | 198 | 53 (29–70) | 4 | PARP-1 | Neoadj. Ant/Tax | IHC | OS: 4.30 (0.74–25.00) PFS: 1.18 (1.03–1.35) | 8 | |
Mazzotta [13] | 2016 | Italy | Caucasian | 1998–2012 | IDC/others Stage I-IIIB | 114 | 53 | 4.8 | PARP-1 | Adj. Horm/chemo | IHC | OS: 1.59 (1.40–181.19) DFS: 6.61 (1.52–28.80) | 8 | |
Deng [8] | 2017 | China | Asian | 2000–2012 | TNBC Stage I-IIIB | 118 | 51.6 (25–81) | 6.2 | PARP-1 | Adj. Ant/Tax | IHC | DFS: 2.23 (1.20–4.13) | 8 | |
Mangia [12] | 2017 | Italy | Caucasian | 1996–2012 | IDC/ILC/ others NA | 308 | 51 (24–80) | 6.1 | PARP-1 | NA | IHC | OS: 1.71 (0.36–8.16) DFS: 0.78 (0.32–1.91) | 8 | |
Song [19] | 2017 | China | Asian | 2005–2010 | IDC, LC, MC Stage I-IV | 547 | 51 (20–82) | 9.8 | PARP-3 | Adj. CAF/CEFD | IHC | OS: 1.71 (0.93–3.15) DFS: 1.94 (1.19–3.19) | 8 | |
Siraj [18] | 2018 | Saudi Arabia | Caucasian | 1990–2011 | IDC, ILC, MC Stage I–IV | 1008 | 45 (39–54) | 4 | PARP | NA | IHC | OS: 1.43 (1.01–2.04) | 8 | |
Ovary | Brustmann [22] | 2007 | Austria | Caucasian | 1985–1996 | SOC Stage I–III | 50 | 64 | NA | PARP | Adj. PBC | IHC | DFS: 1.16 (1.02–1.31) | 7 |
Barnett [21] | 2010 | USA | Caucasian | 1995–2003 | SOC Stage I–IV | 186 | 61 (19–86) | NA | PARP | Adj. PBC | IHC | OS: 0.71 (0.50–0.99) PFS: 0.36 (0.09–1.51) | 7 | |
Gan (1) * [23] | 2013 | UK | Caucasian | 1991–2007 | SOC Stage I–IV | 174 | 61 (36–86) | NA | PARP-1 | Adj. PBC | IHC | OS: 1.90 (1.10–3.20) PFS: 2.59 (1.12–6.00) | 7 | |
Gan (2) * [23] | 2013 | UK | Caucasian | 1991–2007 | SOC Stage I–IV | 174 | 61 (36–86) | NA | C-PARP-1 | Adj. PBC | IHC | OS: 1.63 (1.04–2.57) PFS: 1.20 (1.00–1.44) | 7 | |
Ali [20] | 2019 | UK | Caucasian | 1997–2010 | SOC Stage I–IV | 525 | NA | NA | PARP-1 | Adj. PBC | IHC | PFS: 1.13 (0.83–1.54) | 7 | |
Molnar [24] | 2020 | Hungary | Caucasian | 2011–2017 | SOC Stage IIIA-IIIB | 86 | 57 | 2.7 | PARP | Adj. Pac/Carbo | IHC | OS: 11.74 (1.30–105.63) PFS: 13.52 (1.86–98.04) | 8 | |
Molnar [25] | 2021 | Hungary | Caucasian | 2011–2019 | SOC Stage IIIA-IIIB | 104 | 57.9 | 2.8 | PARP | Adj. Pac/Carbo | IHC | OS: 1.14 (1.03–1.27) PFS: 1.05 (1.02–1.07) | 8 | |
Lung | Kim [27] | 2014 | South Korea | Asian | 2008–2012 | SCLC Stage I–III | 79 | 62 | 1.6 | PARP-1 | Neoadj. Eto/Cis/Carbo | IHC | PFS: 0.49 (0.26–0.91) | 8 |
Xie [28] | 2014 | China | Asian | 2008–2010 | NSCLC Stage I–IV | 111 | 63 (43–81) | NA | PARP-1 | NA | IHC | OS: 2.29 (1.08–4.85) | 7 | |
Michels [26] | 2015 | France | Caucasian | 1994–2002 | NSCLC Stage I-II | 225 | 64 (40–82) | 10.03 | PARP | NA | IHC | OS: 1.99 (1.04–3.76) DFS: 1.71 (0.95–3.62) | 8 | |
Liver | Lin [29] | 2016 | China | Asian | 2005–2008 | HCC Stage I–IV | 145 | 45.4 | NA | PARP-2 | NA | IHC | OS: 4.56 (2.12–9.79) | 7 |
Yu [30] | 2019 | China | Asian | NA | HCC Stage I–IV | 298 | NA | NA | PARP-1 | NA | PCR | OS: 2.43 (1.17–5.07) DFS: 2.11 (1.46–3.04) | 7 | |
Soft tissue | Li [31] | 2016 | China | Asian | 1996–2012 | SC NA | 50 | 55.1 (24–90) | 5.4 | PARP-1 | NA | IHC | DFS: 1.07 (1.02–1.14) | 7 |
Kim [37] | 2016 | South Korea | Asian | 1998–2013 | STS Stage I–IV | 105 | NA | 15 | PARP-1 | Adj. chemo | IHC | DFS: 2.78 (1.70–4.55) | 8 | |
Brain | Murnyák [32] | 2017 | Hungary | Caucasian | 2006–2014 | Glioma Stage II-IV | 135 | 60.5 (21–89) | NA | PARP-1 | NA | PCR | OS: 1.11 (1.01–1.22) | 7 |
Oesophagus | Yamamoto [33] | 2017 | Japan | Asian | 1998–2011 | SCC IA-IVB | 86 | NA | 3.5 | PARP-1 | NA | IHC | OS: 2.39 (1.29–4.44) | 8 |
Pancreas | Klauschen [35] | 2012 | Germany | Caucasian | NA | PDAC Stage I–IV | 178 | NA | NA | PARP | NA | IHC | OS: 0.63 (0.41–0.96) | 7 |
Skin | Donizy [36] | 2020 | USA | Caucasian | 1989–2018 | MM Stage I–IV | 192 | 65 | 1.9 | PARP-1 | NA | IHC | OS:1.53 (1.01–2.33) | 8 |
Stomach | Liu [34] | 2016 | China | Asian | NA | GC stage I–IV | 564 | 60 (29–82) | 5.5 | PARP-1 | NA | IHC | OS: 1.64 (0.99–2.71) DFS: 1.35 (0.86–2.12) | 8 |
Organ | Study, Year | Format of Sampling | IHC Evaluation Method | Antibody | No. of Involved Pathologists | IHC Cut-Off Value | Localisation | Number of High PARP Cases (%) | ||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Company | Source | Type | Clone | Dilution | ||||||||
Breast | Minckwitz, 2011 [16] | TMA | IRS | BD Pharmingen | Mouse | mAb | 7D3-6 | 1:1500 | 2 * | 6 | Cytoplasm | 151 (23.7) |
Rojo, 2012 [17] | TMA | Computer based scoring | Abcam | Mouse | mAb | A6.4.12 | 1:300 | 1 | NA (29–133.094) | Nuclear | 103 (31.2) | |
Donizy, 2014 [9] | TMA | IRS | Abcam | Rabbit | pAb | ab6079 | 1:150 | 2 | 6 | Cytoplasm and Combined N&C | 48 (57.8) 35 (42.2). | |
Aiad (1), 2015 [7] | NCBs | H score | eBioscience | Mouse | mAb | C2-10 | 1:100 | 3 | 70 | Cytoplasm | 40 (48.0) | |
Aiad (2), 2015 [7] | NCBs | H score | eBioscience | Mouse | mAb | C2-10 | 1:100 | 3 | 10 | Nuclear | 64 (76.0) | |
Green, 2015 [11] | TMA | H score | BD Pharmingen | Mouse | mAb | 7D3-6 | 1:1000 | 2 * | 10 | Nuclear | 524 (41.2) | |
Park, 2015 [14] | TMA | Allred score | Santa Cruz Biotechnology | Mouse | mAb | F-2, sc-8007 | 1:100 | 2 | 13 | Nuclear | 78 (41.0) | |
Zhai, 2015 [15] | WTS | QS | Santa Cruz Biotechnology | Mouse | mAb | F-2, sc-8007 | 1:300 | 7 * | 10 | Nuclear | 59 (54.6) | |
Mazzotta, 2016 [13] | WTS | QS | Santa Cruz Biotechnology | Mouse | mAb | F-2, sc-8007 | 1:500 | 2 | 10 | Nuclear | 68 (59.6) | |
Deng, 2017 [8] | WTS | QS | Abcam | Rabbit | pAb | ab6079 | NA | 3 * | 10 | Nuclear | 52 (44.1) | |
Mangia, 2017 [12] | TMA | QS | Santa Cruz Biotechnology | Mouse | mAb | F-2, sc-8007 | 1:500 | 2 | 10 | Nuclear | 76 (28.9) | |
Siraj, 2018 [18] | TMA | QS | Cell signaling | Rabbit | mAb | D64E10 | NA | 2 * | 10 | Nuclear | 451 (44.7) | |
Song, 2017 [19] | WTS | H score | Abcam | Rabbit | pAb | 96601 | 1:100 | 2 | 57.5 | Nuclear | 234 (47.5) | |
Ovary | Brustmann, 2007 [22] | TMA | IRS | Novocastra | Mouse | mAb | NA | 1:30 | 1 | 8 | Nuclear | 38 (76.0) |
Barnett, 2010 [21] | WTS | IRS | NeoMarkers Fremont | Mouse | mAb | A6.4.12 | 1:200 | 1 | 8 | Nuclear | 101 (54.0) | |
Gan (1), 2013 [23] | TMA | H score | BD Pharmingen | Mouse | mAb | 7D3-6 | 1:600 | 1 | 180 | Nuclear | 33 (22.0) | |
Gan (2), 2013 [23] | TMA | H score | Abnova | Mouse | mAb | A6.4.12 | 1:600 | 1 | 75 | Nuclear | 117 (79.0) | |
Ali, 2019 [20] | TMA | H score | Cell signaling | Rabbit | mAb | 46D11 | 1:600 | 3 * | 80 | Nuclear | 208 (51.9) | |
Molnar, 2020 [24] | WTS | SI based scoring | Abcam | Rabbit | pAb | Ab6079330 | 1:500 | 1 * | 1 | Nuclear | 45 (52.3) | |
Molnar, 2021 [25] | WTS | SI based scoring | Abcam | Rabbit | pAb | Ab6079330 | 1:500 | 1 * | 1 | Nuclear | 70 (67.3) | |
Lung | Kim, 2014 [27] | WTS | SP based scoring | Bethyl Laboratories Inc. | Rabbit | pAb | 00279 | 1:200 | 1 * | 3 | Nuclear | 33 (41.8) |
Xie, 2014 [28] | WTS | IRS | Biorbyt | Rabbit | pAb | NA | 1:300 | 2 | 4 | Nuclear | 62 (55.9) | |
Michels, 2015 [26] | WTS | H score | Merck | Mouse | mAb | 10H | 1:1500 | 3 * | 145 * | Nuclear | 49 (53.3) | |
Liver | Lin, 2016 [29] | WTS | SI based scoring | Raybiotech, Inc | Goat | NA | Q9UGN5 | NA | NA | 2 | Nuclear | 75 (51.7) |
Soft tissue | Li, 2016 [31] | WTS | Summation based scoring | Abcam | Rabbit | pAb | ab6079 | 1:50 | NA | 3 | Combined N&C | 39 (78.0) |
Kim, 2016 [37] | TMA | Allred score | Santa Cruz Biotechnology | Mouse | mAb | F-2 sc-8007 | 1:100 | 3 | 10 | Nuclear | 64 (57.1) | |
Oesophagus | Yamamoto, 2017 [33] | WTS | SI based scoring | Santa Cruz Biotechnology | Mouse | mAb | F2, sc-8007 | 1:50 | 2 | 2 | Nuclear | 54 (62.8) |
Pancreas | Klauschen, 2012 [35] | TMA | IRS | BD Pharmingen | Mouse | mAb | 7D3-6 | 1:1000 | 2 | 3 | Nuclear | 138 (77.5) |
Skin | Donizy, 2020 [36] | WTS | H score | Santa Cruz Biotechnology | Mouse | mAb | sc-74470 (B10) | 1:50 | 1 | 200 | Nuclear | 72 (43.0) |
Stomach | Liu, 2016 [34] | TMA | H score | Abcam | Rabbit | pAb | ab6079 | 1:200 | 2 | 175 | Nuclear | 266 (47.2) |
Parameters | Number of Studies | Number of Patients | Pooled OR (95% CI) | p-Value | Heterogeneity | ||
---|---|---|---|---|---|---|---|
I2 (%) | p-Value | Model | |||||
Clinicopathological parameters | |||||||
Age (<50 vs. >50) | 8 | 2977 | 0.96 (0.82–1.12) | 0.59 | 44 | 0.08 | Fixed |
Tumour size (<5 cm vs. >5 cm) | 8 | 2453 | 1.60 (1.32–1.95) | <0.001 * | 80 | < 0.001 | Fixed |
Histologic grade (1 + 2 vs. 3) | 16 | 4927 | 1.79 (1.58–2.04) | <0.001 * | 72 | < 0.001 | Fixed |
T stage (1 + 2 vs. 3+4) | 4 | 1460 | 1.26 (0.91–1.75) | 0.16 | 14 | 0.32 | Fixed |
Lymph node metastasis (absent vs. present) | 17 | 3743 | 1.27 (1.10–1.46) | 0.001 * | 42 | 0.03 | Fixed |
Distant metastasis (absent vs. present) | 6 | 1668 | 2.40 (1.79–3.23) | <0.001 * | 61 | 0.03 | Fixed |
TNM stage (I + II vs. III + IV) | 6 | 2260 | 1.49 (1.24–1.79) | <0.001 * | 0 | 0.94 | Fixed |
Lympho-vascular invasion (absent vs. present) | 10 | 3141 | 1.22 (1.05–1.42) | 0.01 * | 62 | 0.004 | Fixed |
Immunohistological markers | |||||||
Ki-67 (negative vs. positive) | 5 | 2529 | 1.60 (1.35–1.90) | <0.001 * | 83% | < 0.001 | Fixed |
BRCA1 (negative vs. positive) | 4 | 1546 | 1.63 (1.32–2.02) | <0.001 * | 89% | < 0.001 | Fixed |
BRCA2 (negative vs. positive) | 3 | 1040 | 2.78 (1.94–3.98) | <0.001 * | 92% | < 0.001 | Fixed |
Parameters | No. of Studies/Cohorts | Begg Test (p-Value) | Egger Test (p-Value) | Model |
---|---|---|---|---|
PARPs and survival outcomes | ||||
Overall Survival | 24/26 | 0.133 | 0.024 * | Fixed |
Disease-free survival | 14 | 0.062 | 0.001 * | Fixed |
Progression-free survival | 7/8 | 0.536 | 0.455 | Fixed |
PARPs and clinicopathological parameters | ||||
Age (>50 vs. <50) | 8 | 0.063 | 0.017 * | Fixed |
Tumour size (>5 cm vs. <5 cm) | 8 | 1.000 | 0.723 | Fixed |
Histologic grade (1 + 2 vs. 3) | 4 | 0.308 | 0.345 | Fixed |
T stage (1 + 2 vs. 3 + 4) | 17 | 0.964 | 0.532 | Fixed |
Lymph node metastasis (absent vs. present) | 6 | 1.000 | 0.804 | Fixed |
Distant metastasis (absent vs. present) | 6 | 0.259 | 0.354 | Fixed |
TNM stage (I + II vs. III + IV) | 10 | 1.000 | 0.513 | Fixed |
PARPs and Immunohistological markers | ||||
Ki-67 (negative vs. positive) | 5 | 0.220 | 0.113 | Fixed |
BRCA1 (negative vs. positive) | 4 | 0.308 | 0.368 | Fixed |
BRCA2 (negative vs. positive) | 3 | 1.000 | 0.370 | Fixed |
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Thakur, N.; Yim, K.; Abdul-Ghafar, J.; Seo, K.J.; Chong, Y. High Poly(ADP-Ribose) Polymerase Expression Does Relate to Poor Survival in Solid Cancers: A Systematic Review and Meta-Analysis. Cancers 2021, 13, 5594. https://doi.org/10.3390/cancers13225594
Thakur N, Yim K, Abdul-Ghafar J, Seo KJ, Chong Y. High Poly(ADP-Ribose) Polymerase Expression Does Relate to Poor Survival in Solid Cancers: A Systematic Review and Meta-Analysis. Cancers. 2021; 13(22):5594. https://doi.org/10.3390/cancers13225594
Chicago/Turabian StyleThakur, Nishant, Kwangil Yim, Jamshid Abdul-Ghafar, Kyung Jin Seo, and Yosep Chong. 2021. "High Poly(ADP-Ribose) Polymerase Expression Does Relate to Poor Survival in Solid Cancers: A Systematic Review and Meta-Analysis" Cancers 13, no. 22: 5594. https://doi.org/10.3390/cancers13225594