p53 Status Correlates with the Risk of Recurrence in Non-Muscle Invasive Bladder Cancers Treated with Bacillus Calmette–Guérin: A Meta-Analysis

<div><p>Objective</p><p>Published studies have yielded inconsistent results on the relationship between p53 status and the prognosis of non-muscle invasive bladder cancer (NMIBC) treated with Bacillus Calmette–Guérin (BCG) intravesical therapy. Therefore, we performed a meta-analysis to evaluate the prognostic value of p53 in NMIBC treated with BCG.</p><p>Methods</p><p>We systematically searched for relevant literature in PubMed, EMBASE, CNKI, and Chinese Wanfang databases. Hazard ratios (HRs) with 95% confidence intervals (CIs) were combined as the effect size (ES) across studies for recurrence-free survival (RFS) and progression-free survival (PFS).</p><p>Results</p><p>A total of 11 studies, consisting of 1,049 participants, met the criteria. Overall, there was no clear relationship between p53 status and RFS or PFS for NMIBC patients treated with BCG (HR: 1.40, 95% CI: 0.91-2.16; HR: 1.37, 95% CI: 0.90-2.09, respectively). Obvious heterogeneity was observed across the studies (I² = 69.5%, <i>P</i> = 0.001; I² = 44.7%, <i>P</i> = 0.081, respectively). In stratified analysis by region, p53 overexpression was a predictor of poor RFS in Asian populations (HR: 1.57, 95% CI: 1.08-2.27). In addition, after excluding the studies that possibly contributed to the heterogeneity by the Galbraith plot, the overall association for RFS became statistically significant (HR: 1.38 95% CI: 1.08-1.77) without evidence of heterogeneity (I² = 0.0%, <i>P</i> = 0.499).</p><p>Conclusion</p><p>This meta-analysis suggests that p53 overexpression in NMIBC patients treated with BCG may be associated with RFS, especially in Asian populations. Because of the heterogeneity and other limitations, further studies with rigid criteria and large populations are still warranted to confirm our findings.</p></div

Subgroup results of RFS and heterogeneity test.

<p>Subgroup results of RFS and heterogeneity test.</p

Nutrient use efficiency of poplar and several plantation tree species in southern China.

<p>^a Cutting age of plantations in China are as follows: poplar, 12–15 years; Chinese fir, 25–30 years; <i>Eucalyptus</i>, 5–10 years; <i>Pinus massoniana</i>, 30–40 years; <i>Acacia mangium</i>, 10–15 years.</p><p>^b NUE1 = aboveground biomass of trees (t)/nutrient content (kg) in aboveground parts of trees.</p><p>^c NUE2 = stemwood biomass of trees (t)/nutrient content (kg) in tree stemwood.</p><p>Nutrient use efficiency of poplar and several plantation tree species in southern China.</p

Subgroup results of RFS and heterogeneity test.

<p>Subgroup results of RFS and heterogeneity test.</p

Relationship between stand volume and stand age in <i>P</i>. <i>deltoides</i> plantation in Zhoushan Forestry Farm, Jiangsu, China.

<p>Error bars represent standard error (SE).</p

Main characteristics of all studies included in this meta-analysis.

<p>No., number; NMIBC, non-muscle-invasive bladder cancer; RFS, recurrence-free survival; PFS, progression-free survival.</p><p>Main characteristics of all studies included in this meta-analysis.</p

Galbraith plot analysis was used to evaluate heterogeneity.

<p>It suggested that two studies were the potential source of heterogeneity for RFS (A), while one for PFS (B).</p

Flowchart of study selection.

<p>Flowchart of study selection.</p

Current annual increment and mean annual increment of stand volume of <i>P</i>. <i>deltoides</i> plantation at Zhoushan Forestry Farm, Jiangsu, China.

<p>Error bars represent standard error (SE).</p

Nutrient cycling of aboveground poplar and Chinese fir at different maturity stages.

<p>^aAnnual nutrient increment + annual nutrient return</p><p>^b∑ (annual biomass increment of each poplar tissue × nutrient concentration of each tissue)</p><p>^c∑ (aboveground litterfall biomass of poplar of each month in the stand × nutrient concentration in litterfall of each month)</p><p>^d(annual nutrient return / annual nutrient uptake) ×100%; ^e data are from Sheng and Fan (2005).</p><p>Nutrient cycling of aboveground poplar and Chinese fir at different maturity stages.</p