Effect of TP53 mutation, expression and polymorphism on the survival, immune infiltration and ferroptosis in patients with prostate cancer.

Tumor protein 53 (TP53) serves a key role in the prevention of tumor formation, while TP53 mutation can lead to uncontrolled cell division and tumorigenesis. Men carrying TP53 mutations have a higher risk of developing invasive prostate cancer. Notably, there are distinct epidemiological and genomic features between Chinese and Western patients with prostate cancer, wherein TP53 mutations are more prevalent among Chinese patients. However, the effect of TP53 mutations, expression and polymorphisms on prostate cancer remain to be elucidated. Therefore, in the present study, bioinformatics analyses and meta-analysis were conducted to assess how TP53 mutations and expression affect the prognosis and tumor microenvironment in patients with prostate cancer. Additionally, the role of TP53 in ferroptosis was also investigated in vitro. The results indicated that high TP53 expression was a prognostic factor associated with poor outcomes in patients with prostate cancer. In addition, bioinformatics analysis using The Cancer Genome Atlas database demonstrated significant differences in immune cell infiltration and in the expression of ferroptosis-related genes between wild-type and mutant TP53 prostate cancer tissues, as well as between high and low TP53-expressing tumors. Furthermore, erastin, a well-known inducer of ferroptosis, triggered ferroptosis in prostate cancer cells via downregulation of solute carrier family 7 member 11 and glutathione peroxidase 4, independent of TP53 expression. However, reactive oxygen species levels were markedly higher in TP53-expressing cells, LnCAP and DU145, compared with TP53-null cells, PC3 cells. Overall, the results of the present study could provide a potential novel therapeutic target for the treatment of prostate cancer in the future.