A new survival model based on ferroptosis-related genes (FRGS) for prognostic prediction in bladder cancer

Actas Urol Esp (Engl Ed). 2022 Oct;46(8):494-503. doi: 10.1016/j.acuroe.2022.06.001. Epub 2022 Jun 29.
[Article in English, Spanish]

Abstract

Background: Bladder cancer (BLCA) is a malignant urothelial carcinoma with a high mortality rate. Ferroptosis is a new type of programmed cell death and functions in suppressing tumor growth and progression. However, few studies focus on ferroptosis and BLCA.

Materials and methods: We explored the potential oncogenic roles of ferroptosis-related genes in BLCA based on multiple public datasets. We then used univariate and multivariate cox regression to build a new survival model based on ferroptosis-related genes to predict the survival of BLCA.

Results: We found that 23 ferroptosis-related genes had a strong correlation with each other in BLCA. Eight ferroptosis-related genes, CDKN1A, HSPA5, NFE2L2, MT1G, FANCD2, CISD1, TFRC, NCOA4, had a significantly different expression and heat-map. HSPA5 and CISD1 have a statistically significant difference in OS and DFS. Besides, CISD1 had an ideal nomogram to predict the 1-3-5-year OS (C-index: 0.701, P < .001). Furthermore, HSPA5 and CISD1 had a lower DNA methylation rate than normal tissue and HSPA5 had a positive connection with TMB (P = .02). In addition, HSPA5 participated in the DNA replication and P53 signaling pathway, and CISD1 mediated the oxidative phosphorylation and positive regulation of the intrinsic apoptotic signaling pathway.

Conclusion: Ferroptosis-related genes had a strong correlation with BLCA, notably, HSPA5 and CISD1 may play a role in inducing ferroptosis to suppress bladder tumorigenesis and CISD1 can be a novel prognostic biomarker as well as an effective target for diagnosis and treatment in BLCA.

Keywords: Biomarcador; Biomarker; Bladder cancer; CISD1; Cáncer de vejiga; Ferroptosis; HSPA5; Modelo de supervivencia; Survival model.

MeSH terms

  • Biomarkers
  • Carcinoma, Transitional Cell*
  • Ferroptosis* / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Prognosis
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • Urinary Bladder Neoplasms* / genetics
  • Urinary Bladder Neoplasms* / pathology

Substances

  • Biomarkers
  • Tumor Suppressor Protein p53