Evaluation of the Prognostic Role of TP53 Gene Mutations in Prostate Cancer Outcome: A Systematic Review and Meta-Analysis

Introduction

Prostate cancer, 1 of the most common cancers in men, is influenced by age, genetics, race, and lifestyle. The TP53 gene, encoding the p53 protein crucial for cell cycle regulation and DNA repair, is frequently mutated in metastatic prostate cancers. These mutations impact prognosis and resistance to treatments, underscoring the role of genetic factors in disease progression and therapeutic challenges.

Methods

Databases such as PubMed, Scopus, and ISI were searched using the keywords "prostate cancer," "P53," "TP53," "survival," and "prognosis," along with manual searches in other sources. Initial screening and selection of articles were conducted independently and blinded by 2 reviewers, focusing on titles abstracts, and full texts when necessary. The Newcastle-Ottawa Scale (NOS) was used for full-text evaluation. Data were analyzed using STATA 11, with heterogeneity assessed using the I² index.

Results

Overall survival (OS) for prostate cancer patients with TP53 mutations was approximately 13% lower than for those without mutations at 1 year, 20% lower at 3 years, and 16% lower at 5 years. TP53 mutations were also associated with faster disease progression and a 15% reduction in progression-free survival (PFS) over 1 year. The hazard ratio (HR) for death in patients with TP53 mutations was 1.76, and for PFS, it was 1.62, indicating a 76% increased risk of death and a 62% increased risk of disease progression.

Conclusion

TP53 mutations are associated with shorter survival and faster disease progression in prostate cancer, underscoring the importance of precise evaluation and management of these mutations in treatment.