Review Article
Prognostic and Clinicopathological Significance of Downregulated p16 Expression in Patients with Bladder Cancer: A Systematic Review and Meta-Analysis
Table 2
Main meta-analysis results of p16 expression in patients with bladder cancer.
| | Analysis | No. (No.) | HR (95% CI) | | | Model | Heterogeneity | Publication bias | | % | | Begg’s | Egger’s |
| | RFS | 18 (1032) | 1.63 (1.36–1.94) | 5.40 | | F | 42.6 | 0.029 | 0.405 | 0.246 | | Europe | 8 (365) | 1.90 (1.13–3.19) | 2.43 | | R | 53.1 | 0.037 | 1.000 | 0.749 | | Asia | 9 (547) | 1.44 (1.15–1.81) | 3.15 | | F | 30.7 | 0.173 | 0.348 | 0.020 | | America | 1 (120) | 1.58 (0.77–3.25) | 1.24 | | F | 0.0 | / | / | / | | Ta–T1 | 8 (430) | 1.96 (1.23–3.14) | 2.82 | | R | 55.5 | 0.028 | 0.711 | 0.916 | | Ta–T4 | 10 (602) | 1.41 (1.12–1.77) | 2.96 | | F | 10.2 | 0.348 | 1.000 | 0.062 | | G1-G2 | 2 (75) | 4.12 (2.48–6.83) | 5.49 | | F | 0.0 | 0.924 | 1.000 | / | | G1–G3 | 14 (762) | 1.44 (1.18–1.75) | 3.50 | | F | 11.9 | 0.323 | 0.584 | 0.031 | | G2-G3 | 2 (95) | 1.37 (0.78–2.42) | 1.10 | | F | 0.0 | 0.802 | 1.000 | / | | Cut-off value (≤10%) | 13 (741) | 1.83 (1.34–2.51) | 3.79 | | R | 54.8 | 0.009 | 0.583 | 0.297 | | Cut-off value (>10%) | 5 (291) | 1.34 (0.86–2.09) | 1.28 | | F | 0.0 | 0.701 | 0.462 | 0.166 | | OS | 9 (425) | 1.70 (1.16–2.50) | 2.71 | | F | 0.0 | 0.584 | 0.602 | 0.165 | | Europe | 4 (167) | 2.54 (1.05–6.15) | 2.07 | | F | 27.0 | 0.250 | 1.000 | 0.289 | | Asia | 4 (208) | 1.61 (0.97–2.66) | 1.85 | | F | 0.0 | 0.703 | 0.734 | 0.166 | | America | 1 (50) | 1.41 (0.62–3.19) | 0.83 | | F | 0.0 | / | / | / | | Ta–T4 | 5 (230) | 1.59 (0.98–2.60) | 1.87 | | F | 3.1 | 0.389 | 1.000 | 0.232 | | Ta–T1 | 2 (122) | 1.57 (0.32–7.75) | 0.55 | | F | 0.0 | 0.750 | 1.000 | / | | T2–T4 | 2 (73) | 1.96 (0.99–3.88) | 1.94 | | R | 52.1 | 0.148 | 1.000 | / | | G1–G3 | 7 (353) | 1.82 (1.16–2.84) | 2.62 | | F | 3.9 | 0.397 | / | / | | L | 1 (22) | 1.41 (0.18–10.90) | 0.33 | | F | / | / | / | / | | H | 1 (50) | 1.41 (0.62–3.19) | 0.83 | | F | / | / | / | / | | Cut-off value (≤10%) | 7 (278) | 1.83 (1.17–2.86) | 2.63 | | F | 3.2 | 0.402 | 0.764 | 0.185 | | Cut-off value (>10%) | 2 (147) | 1.40 (0.66–2.96) | 0.87 | | F | 0.0 | 0.951 | 1.000 | / | | PFS | 8 (470) | 2.18 (1.37–3.48) | 3.28 | | F | 26.3 | 0.219 | 0.174 | 0.325 | | IHC | 6 (347) | 1.84 (1.13–3.01) | 2.44 | | F | 0.0 | 0.487 | 1.000 | 0.754 | | FISH | 2 (123) | 11.28 (2.45–51.83) | 3.11 | | F | 0.0 | 0.718 | 1.000 | / | | Europe | 5 (297) | 2.09 (1.21–3.63) | 2.62 | | F | 0.0 | 0.484 | 1.000 | 0.607 | | America | 1 (50) | 1.14 (0.39–3.31) | 0.24 | | F | / | / | / | / | | Ta–T1 | 5 (297) | 2.09 (1.21–3.63) | 2.62 | | F | 0.0 | 0.484 | 1.000 | 0.607 | | T2–T4 | 1 (50) | 1.14 (0.39–3.31) | 0.24 | | F | / | / | / | / | | G1–G3 | 5 (297) | 2.09 (1.21–3.63) | 2.62 | | F | 0.0 | 0.484 | 1.000 | 0.607 | | H | 1 (50) | 1.14 (0.39–3.31) | 0.24 | | F | / | / | / | / | | Cut-off value (≤10%) | 4 (200) | 2.61 (1.42–4.77) | 3.10 | | F | 0.0 | 0.932 | 1.000 | 0.746 | | Cut-off value (>10%) | 2 (147) | 0.95 (0.41–2.18) | 0.13 | | F | 0.0 | 0.579 | 1.000 | / | | DSS/CSS | 3 (187) | 1.52 (0.85–2.71) | 1.42 | | F | 0.0 | 0.825 | 0.296 | 0.517 |
| | Clinicopathological parameters | | OR (95% CI) | | | | | | | |
| | Stage (T2–T4 versus Ta–T1) | 19 (1231) | 3.13 (2.42–4.06) | 8.63 | | F | 1.4 | 0.440 | 0.529 | 0.377 | | Asia | 14 (878) | 3.41 (2.51–4.64) | 7.87 | | F | 0.0 | 0.800 | 0.661 | 0.650 | | Europe | 3 (277) | 3.17 (1.79–5.60) | 3.96 | | F | 63.7 | 0.064 | 1.000 | 0.994 | | America | 2 (76) | 1.15 (0.41–3.20) | 0.26 | | F | 0.0 | 0.604 | 1.000 | / | | Stage (T1 versus Ta) | 5 (374) | 1.55 (0.87–2.76) | 1.50 | | F | 40.5 | 0.152 | 0.806 | 0.402 | | Grade (G3 versus G1-2) | 20 (1291) | 3.33 (2.51–4.42) | 8.32 | | F | 0.0 | 0.519 | 0.206 | 0.805 | | Asia | 15 (895) | 3.36 (2.44–4.63) | 7.41 | | F | 18.6 | 0.246 | / | / | | Europe | 3 (196) | 2.62 (1.23–5.57) | 2.50 | | F | 0.0 | 0.984 | / | / | | America | 2 (200) | 4.51 (1.61–12.61) | 2.87 | | F | 0.0 | 0.659 | / | / | | Grade (H versus L) | 8 (688) | 1.20 (0.62–2.33) | 0.55 | | R | 61.8 | 0.011 | 0.063 | 0.080 | | Lymph node metastasis (yes versus no) | 5 (319) | 2.20 (1.26–3.83) | 2.77 | | F | 27.2 | 0.240 | 1.000 | 0.487 | | Muscle Invasive (yes versus no) | 4 (248) | 2.18 (0.72–6.62) | 1.38 | | R | 71.8 | 0.014 | 0.497 | 0.998 | | Number of tumors (multiple versus single) | 2 (166) | 1.11 (0.43–2.85) | 0.22 | | F | 0.0 | 0.984 | 1.000 | / | | Tumor size (>3 versus ≤3) | 2 (193) | 2.93 (0.40–21.36) | 1.06 | | R | 79.2 | 0.028 | 1.000 | / |
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RFS: recurrence-free survival; OS: overall survival; PFS: progression-free survival; DSS: disease-specific survival; CSS: cancer-specific survival; HR: hazard ratio; OR: odds ratio; CI: confidence interval; No.: number of studies; No.: number of patients; : for the heterogeneity; F: fixed-effect model; R: random-effect model; L: low grade; H: high grade.
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