Author Identifier

Qi Yang: http://orcid.org/0000-0003-2919-6142

Date of Award

2025

Document Type

Thesis - ECU Access Only

Publisher

Edith Cowan University

Degree Name

Doctor of Philosophy

School

School of Medical and Health Sciences

First Supervisor

Elin Gray

Second Supervisor

Aaron Beasley

Third Supervisor

Song Wu

Abstract

Bladder cancer is a common and aggressive malignancy. Treatments like surgery, radiation, immunotherapy, and cisplatin-based chemotherapy have improved patient outcomes, but high recurrence and metastasis rates still lead to poor survival. Ferroptosis, a regulated cell death (RCD) mechanism identified in 2012, shows potential for selectively eliminating cancer cells. Although ferroptosis has been increasingly studied in bladder cancer, its precise molecular mechanisms and therapeutic potential remain incompletely understood. This research explores the link between ferroptosis and bladder cancer to identify potential therapeutic targets.

The thesis includes a comprehensive review of the mechanisms underlying ferroptosis and explores the potential of ferroptosis-targeted therapies in bladder cancer management. Furthermore, comprehensive bioinformatic analysis of gene expression profiles and clinical data from public databases [The Cancer Genome Atlas Program (TCGA), the Gene Expression Omnibus (GEO), and FerrDb databases] was used to construct a bladder cancer ferroptosis-related prognostic model, and the predictive ability of this model was validated using an independent data set. Among the twelve ferroptosis-related genes (FRGs) included in the model, SLC3A2 was the highest[1]connected protein within the Protein-protein interaction (PPI) network.

SLC3A2 was found to be highly expressed in bladder cancer cell lines, and SLC3A2 knockdown in two bladder cancer cell lines (T24 and UMUC3) reduced cell proliferation, migration, and invasion. Knockdown of SLC3A2 also increased the cisplatin chemotherapy sensitivity of bladder cancer cells.

This PhD project revealed the key role of ferroptosis in bladder cancer and identified SLC3A2 as a regulator of cell growth, migration, invasion, and cisplatin sensitivity. A ferroptosis-related prognostic model was developed and validated using bioinformatic analysis, providing a tool for predicting bladder cancer outcomes. Targeting SLC3A2 could potentially improve cisplatin sensitivity, highlighting ferroptosis-based therapeutic possibilities.

DOI

10.25958/qeb3-cr32

Access Note

Access to this thesis is embargoed until 7th August 2030

Available for download on Wednesday, August 07, 2030

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