Prognostic and Clinicopathological Significance of Downregulated p16 Expression in Patients with Bladder Cancer: A Systematic Review and Meta-Analysis

p16, encoded by the CDKN2A gene, is a tumor suppressor that has been widely studied in cancer research. However, the relationship of p16 with prognostic and clinicopathological parameters in patients with bladder cancer remains unclear. Data inclusion criteria were articles reporting on the relationship between p16 expression and the prognosis or clinicopathology in patients with bladder cancer. Meta-analyses were performed with Stata software. Hazard ratios (HRs) or odds ratios (ORs) and 95% confidence intervals (95% CI) were calculated to evaluate the relative risks. The source of heterogeneity was analyzed by subgroup analysis. A total of 37 studies with 2246 cases were included and analyzed. The results identified an important link between downregulated p16 expression and poor prognosis in patients with bladder cancer in terms of recurrence-free survival (RFS), overall survival (OS), progression-free survival (PFS), and some clinicopathological parameters including clinical staging, pathological degree, and lymph node metastasis. Subgroup analysis also showed that low p16 expression could function as a warning sign for RFS and PFS in patients with early-stage (Ta–T1) bladder cancer. In conclusion, p16 might play an essential role in the deterioration of bladder cancer and could serve as a biomarker for the prediction for patients' progression and prognosis.