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

  • Authors:
    • Gui-Min Wen
    • Zhen-Ying Zhao
    • Xiao-Hui Zheng
    • Da-Hua Liu
    • Pu Xia
  • View Affiliations / Copyright

    Affiliations: Department of Community Nursing, College of Nursing, Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China, Department of Pharmacy, Tianjin Union Medical Center, Tianjin 300131, P.R. China, Biological Anthropology Institute, College of Basic Medical Science, Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China
    Copyright: © Wen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 445
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    Published online on: July 17, 2025
       https://doi.org/10.3892/ol.2025.15191
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Abstract

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.
View Figures

Figure 1

Roles of TP53-WT and TP53-MT in the
prognosis and clinicopathological features of patients with
prostate cancer. (A) The OS between patients with TP53-MT and
TP53-WT prostate cancer in the TCGA-PRAD cohort was compared by
Kaplan-Meier curve. (B) The OS between patients with high and low
TP53-expressing prostate cancer in the TCGA-PRAD cohort was
compared using Kaplan-Meier curves. (C) Univariate and multivariate
Cox regression analyses were performed to assess the HRs for OS in
patients with prostate cancer based on TP53 mutation status, stage,
gender and age. (D) Univariate and multivariate Cox regression
analyses were performed to evaluate the HRs for OS based on TP53
expression levels, stage, gender and age. (E) Schoenfeld residual
analysis was performed to evaluate whether the PH assumption of the
Cox model holds for TP53 mutations and expression. TP53, tumor
protein 53; WT, wild-type; MT, mutant; OS, overall survival; TCGA,
The Cancer Genome Atlas; PRAD, prostate adenocarcinoma; HR, hazard
ratio; PH, proportional hazards.

Figure 2

Roles of TP53-WT and TP53-MT in the
immune status of patients with prostate cancer. Comparison of the
proportion of (A) immune cells, (C) TMB and (E) MANTIS score
between the TP53-MT and TP53-WT groups in the TCGA-PRAD cohort.
Comparison of the proportion of (B) immune cells, (D) TMB and (F)
MANTIS score between the high and low TP53 expression groups in the
TCGA-PRAD cohort. Error bars indicate standard deviation.
*P<0.05, **P<0.01. TP53, tumor protein 53; WT, wild-type; MT,
mutant; TMB, tumor mutation burden; MANTIS, Microsatellite Analysis
for Normal-Tumor InStability; TCGA, The Cancer Genome Atlas; PRAD,
prostate adenocarcinoma, ns, no significance; NK, natural
killer.

Figure 3

Key genes associated with p53-WT and
TP53-MT in patients with prostate cancer. (A) Top mutated genes
between the high and low TP53 expression groups in the TCGA-PRAD
cohort. (B) Top mutated driver genes with TP53 as hub gene in the
TCGA-PRAD cohort. GSEA was performed using the R programming 3.3.4.
packages ‘clusterProfiler’ based on the top mutated driver genes
between the (C) TP53-MT and TP53-WT groups, as well as between the
(D) high and low TP53 expression groups in the TCGA-PRAD cohort.
KEGG pathway enrichment analysis demonstrated that significantly
enriched pathways included (E) ‘Ribosome’, (F) ‘Herpes simplex
virus 1 infection’ and (G) ‘Transcriptional misregulation in
cancer’, which were potentially associated with TP53 mutations or
altered expression. WT, wild-type; TP53, tumor protein 53; MT,
mutated; TCGA, The Cancer Genome Atlas; PRAD, prostate
adenocarcinoma; GSEA, gene set enrichment analysis; KEGG, Kyoto
Encyclopedia of Genes and Genomes; TSG, tumor suppressor gene; ATM,
ataxia telangiectasia mutated; MDM2, mouse double minute 2 homolog;
CDKN2A, cyclin-dependent kinase inhibitor 2A; CCND1, cyclin D1;
CDKN1A, cyclin-dependent kinase inhibitor 1A; FBXW7, F-Box and WD
repeat domain containing 7; CCNE1, cyclin E1; RB1, retinoblastoma
1; E2F3, E2F transcription factor 3; cGMP, cyclic guanosine
monophosphate; PKG, protein kinase G; PPAR, peroxisome
proliferator-activated receptor.

Figure 4

Meta-analysis of the TP53 codon 72
polymorphism and OS of patients with prostate cancer. (A) Arg/Arg
vs. Arg/Pro in all patients. (B) Arg/Arg vs. Arg/Pro in Asian
patients. (C) Arg/Arg vs. Arg/Pro in Caucasian patients. (D)
Arg/Arg vs. Pro/Pro in all patients. (E) Arg/Arg vs. Pro/Pro in
Asian patients. (F) Arg/Arg vs. Pro/Pro in Caucasian patients.
Error bars=95% confidence interval of odds ratio. TP53, tumor
protein 53; OS, overall survival; Arg, arginine; Pro, proline; df;
degrees of freedom.

Figure 5

Differentially expressed
ferroptosis-related genes in patients with PRAD. (A) A heatmap of
the differentially expressed ferroptosis-related genes in patients
with PRAD with high and low TP53 expression levels. (B) Expression
levels of the ferroptosis-related genes in the high and low TP53
expression groups of patients with PRAD. G1 and G2 indicate low and
high TP53 expression, respectively. (C) A heatmap of the
differentially expressed ferroptosis-related genes in the WT- and
MT-TP53 groups of patients with PRAD. (D) Expression levels of
ferroptosis-related genes in the TP53-MT and TP53-WT groups of
patients with PRAD. *P<0.05, **P<0.01, ***P<0.001
comparing G1 vs. G2. Error bars=standard deviation. TP53, tumor
protein 53; PRAD, prostate adenocarcinoma; WT, wild-type; MT,
mutated.

Figure 6

Roles and mechanisms of erastin and
TP53 expression in ferroptosis in prostate cancer cells. (A) The
protein expression levels of TP53, SLC7A11 and GPX4 were detected
in erastin-treated LnCAP, DU145 and PC3 cells via western blotting.
(B) Cell viability was assessed by MTT assays. (C) Intracellular
ROS levels were measured using DCFH-DA. Error bars=standard
deviation. n=3. *P<0.05 erastin-treated lnCAP, DU145 and PC3
cells vs. control cells. ★P<0.05 erastin-treated PC3
cells vs. erastin-treated LnCAP and DU145 cells. TP53, tumor
protein 53; SLC7A11, solute carrier family 7 member 11; GPX4,
glutathione peroxidase; LnCAP, lymph node carcinoma of the
prostate; PC3, prostatic small cell carcinoma; ROS, reactive oxygen
species; DCFH-DA; 2′,7′-dichlorodihydrofluorescein diacetate; a.u.,
arbitrary units.
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Copy and paste a formatted citation
Spandidos Publications style
Wen G, Zhao Z, Zheng X, Liu D and Xia P: Effect of TP53 mutation, expression and polymorphism on the survival, immune infiltration and ferroptosis in patients with prostate cancer. Oncol Lett 30: 445, 2025.
APA
Wen, G., Zhao, Z., Zheng, X., Liu, D., & Xia, P. (2025). Effect of TP53 mutation, expression and polymorphism on the survival, immune infiltration and ferroptosis in patients with prostate cancer. Oncology Letters, 30, 445. https://doi.org/10.3892/ol.2025.15191
MLA
Wen, G., Zhao, Z., Zheng, X., Liu, D., Xia, P."Effect of TP53 mutation, expression and polymorphism on the survival, immune infiltration and ferroptosis in patients with prostate cancer". Oncology Letters 30.3 (2025): 445.
Chicago
Wen, G., Zhao, Z., Zheng, X., Liu, D., Xia, P."Effect of TP53 mutation, expression and polymorphism on the survival, immune infiltration and ferroptosis in patients with prostate cancer". Oncology Letters 30, no. 3 (2025): 445. https://doi.org/10.3892/ol.2025.15191
Copy and paste a formatted citation
x
Spandidos Publications style
Wen G, Zhao Z, Zheng X, Liu D and Xia P: Effect of TP53 mutation, expression and polymorphism on the survival, immune infiltration and ferroptosis in patients with prostate cancer. Oncol Lett 30: 445, 2025.
APA
Wen, G., Zhao, Z., Zheng, X., Liu, D., & Xia, P. (2025). Effect of TP53 mutation, expression and polymorphism on the survival, immune infiltration and ferroptosis in patients with prostate cancer. Oncology Letters, 30, 445. https://doi.org/10.3892/ol.2025.15191
MLA
Wen, G., Zhao, Z., Zheng, X., Liu, D., Xia, P."Effect of TP53 mutation, expression and polymorphism on the survival, immune infiltration and ferroptosis in patients with prostate cancer". Oncology Letters 30.3 (2025): 445.
Chicago
Wen, G., Zhao, Z., Zheng, X., Liu, D., Xia, P."Effect of TP53 mutation, expression and polymorphism on the survival, immune infiltration and ferroptosis in patients with prostate cancer". Oncology Letters 30, no. 3 (2025): 445. https://doi.org/10.3892/ol.2025.15191
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