KEY TAKEAWAYS
- The study aimed to assess APOL6 as a biomarker for predicting immunotherapy success in bladder cancer via ferroptosis.
- Researchers concluded APOL6 may predict immunotherapy success and identified the STAT1/APOL6/GPX4 axis as crucial in BLCA.
Immune checkpoint inhibitors are increasingly used to treat bladder cancer, but effective biomarkers for predicting outcomes remain limited. Ferroptosis, a type of immunogenic cell death, has been shown to improve patient response to these therapies. However, the mechanisms by which ferroptosis enhances immunotherapy effectiveness in bladder cancer are not yet fully understood.
Zhiwei Fan and the team aimed to investigate how ferroptosis influences immunotherapy efficacy in bladder cancer and identify effective biomarkers for predicting treatment outcomes.
Researchers analyzed The Cancer Genome Atlas (TCGA) mRNA data using single sample Gene Set Enrichment Analysis (ssGSEA) to identify 2 distinct immunological subtypes. They used these subtypes, along with other public datasets, to identify Apolipoprotein L6 (APOL6) as a potential biomarker for predicting immunotherapy efficacy. They examined APOL6’s immunological correlations and predictive value, and experimentally validated its role in promoting ferroptosis and regulating this process.
The results showed that APOL6 is highly relevant immunologically and marks immunologically active tumors in bladder cancer and other cancers. APOL6 interacts with acyl-coenzyme A synthetase long-chain family member 4 (ACSL4) to mediate immunotherapy efficacy through ferroptosis. Additionally, APOL6 is regulated by signal transducer and activator of transcription 1 (STAT1).
The study concluded that APOL6 has potential as a predictive biomarker for immunotherapy success and identified the STAT1/APOL6/GPX4 axis as a key regulatory mechanism in bladder cancer.
This work was supported by National Natural Science Foundation of China (82200819), Natural Science Foundation of Jiangsu Province (BK20220605) and Jiangsu Innovative and Enterpreneurial Talent Programme (JSSCBS20211600).
Source: https://pubmed.ncbi.nlm.nih.gov/39187773/
Fan Z, Liu Y, Wang X, et al. (2024) “APOL6 predicts immunotherapy efficacy of bladder cancer by ferroptosis.” BMC Cancer. 2024;24(1):1046. Published 2024 Aug 26. doi:10.1186/s12885-024-12820-7
