Identification of KIF14 as a ferroptosis biomarker for predicting the prognosis and immunotherapy efficacy of bladder cancer.

Background: Ferroptosis, a recently recognized form of regulated cell death, plays a prominent role in anti-tumor immunity. However, the potential functions of ferroptosis-related regulators in the prognosis, immune checkpoint genes expression, and immunotherapy efficacy of bladder cancer (BC) have not been systematically studied.

Materials and methods: We systematically evaluated the correlations between ferroptosis levels and prognosis, clinical characteristics, tumor mutation burden (TMB), immune checkpoint gene expression, and immune cell infiltration characteristics. The ferroptosis level of each patient was calculated using principal component analysis based on the expression of prognostic differentially expressed genes. Hub ferroptosis-related genes involved in immunoregulation and immunotherapy efficacy in BC were subsequently identified.

Results: Eighteen ferroptosis regulators were associated with the prognosis of BC. We identified three ferroptosis subgroups, which have different immune cell infiltration characteristics and distinct carcinogenesis-related immune pathways, such as immune cell differentiation, and the PD-L1/PD-1 pathway. High ferroptosis levels and ferroptosis-related gene kinesin family member 14 (KIF14) are closely associated with poor prognosis, tumor mutation burden, immune checkpoint genes expression, and immune cell infiltration. An immunotherapy cohort confirmed that patients with high KIF14 expression demonstrated significant therapeutic and clinical benefits.

Conclusions: The study revealed that ferroptosis level and KIF14 were significantly related to prognosis, immune checkpoint genes expression, immune cell infiltration, and immunotherapy response in BC.