P53 is one of the most frequently mutated genes in colorectal cancer (CRC). The present study was undertaken to provide a solid estimate of the prognostic value of p53 mutations in metastatic CRC patients.
This meta-analysis was done in accordance to the Preferred Reporting Item For Systematic Reviews and Meta-Analysis 2020 guidelines. Studies in English published in the last ten years were searched through PubMed and Google Scholar. Final selection criteria were: 1) association with overall survival, 2) presence of Hazard Ratios (HRs) with 95% Confidence Intervals (CIs). The articles were evaluated for quality and risk of bias using the Newcastle-Ottawa Scale and QUIPS tool, respectively. The meta-analysis was conducted with random-effects model according to the Hartung-Knapp-Sidik-Jonkman method and results were depicted in classical Forest plots. Studies heterogeneity was determined by I and Tau statistics. The relationship between p53 mutation and clinic-pathological variables was examined using the χ test.
Nine articles met the eligibility criteria and went to the final analysis. Sample size ranged from 51 to 1043 patients. All studies were retrospective. The Newcastle Ottawa Scale score was >6 in all studies, QUIPS risk of bias was low in 6, moderate in 3 studies. Only three studies analysed the entire p53 gene coding region. The DNA sequencing technological platforms varied from Sanger to NGS sequencing techniques. The p53 mutational frequencies ranged from 35.0 to 73.0%. A strong association (p<0.0001) emerged between p53 alteration and left-sided CRC. The final pooled HR (p53 mutated vs p53 wild-type tumours) for overall survival was 1.30 (95% CI: 0.75-2.25) at random-effects model.
The available evidence does not support a prognostic role for p53 in metastatic CRC patients. Prospective studies, with larger sample sizes and consistent and harmonized methodology, are needed to explore the prognostic role of p53 in metastatic CRC patients.
Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.
