Iron homeostasis landscape informs patient survival and neoadjuvant chemotherapy response in cancer.
6 affiliations
- 1School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, P. R. China.
- 2Guangdong-Hong Kong-Macao Joint Laboratory for New Drug Screening, School of Pharmacy, The Chinese University of Hong Kong, Hong Kong SAR, P. R. China.
- 3Clinical Pharmacology and Quantitative Science, Genmab Inc., Princeton, NJ, USA.
- 4School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, P. R. China. [email protected].
- 5Guangdong-Hong Kong-Macao Joint Laboratory for New Drug Screening, School of Pharmacy, The Chinese University of Hong Kong, Hong Kong SAR, P. R. China. [email protected].
- 6The Chinese University of Hong Kong, 8th Floor, Lo Kwee-Seong Integrated Biomedical Sciences Building, Area 39, Shatin, N.T. Hong Kong, China. [email protected].
Abstract
Background
Cancer cells frequently alter iron metabolism by increasing uptake or decreasing export, promoting oncogenesis and proliferation. However, the quantitative relationship between iron homeostasis and cancer remains underexplored.Methods and results
We simplified these alterations into measurable changes in the expression levels of iron transport-related genes. We investigated the expression of iron transport-related genes by comparing genomic data of 478 human cancer cell lines to 105 normal tissue samples, as well as analyzing clinically paired 6903 tumor to 709 normal samples. We revealed that cancer cells exhibited increased expression of transferrin receptor 1 (TFR1) or CD44 for iron uptake and decreased expression of ferroportin for iron efflux to favor iron accumulation. Using machine learning, we identified TFR1, CD44, and ferroportin as the top three features consistently associated most with patient survival. We developed a cancer-specific iron risk score (CIRS) using parametric time-to-event models based on RNA-seq data from TFR1, CD44, and ferroportin in 4723 patients spanning 15 cancers. The CIRS, cross-validated in five external datasets, significantly stratified survival risk for various cancers, and predicted chemotherapy response in two independent breast cancer pharmacogenomic datasets.Conclusions
Our study enhances the understanding of the relationship between iron homeostasis, survival, and chemotherapy response, laying the groundwork for iron-targeted therapies.
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BibTeX
@article{fan2026iron,
title = {{Iron homeostasis landscape informs patient survival and neoadjuvant chemotherapy response in cancer.}},
author = {Xiaoqing Fan and Kangna Cao and Xu Steven Xu and Xiaoyu Yan},
journal = {BioData mining},
year = {2026},
month = jul,
doi = {10.1186/s13040-026-00589-3},
url = {https://europepmc.org/article/MED/42902310},
note = {CC BY},
}
RIS
TY - JOUR
TI - Iron homeostasis landscape informs patient survival and neoadjuvant chemotherapy response in cancer.
AU - Xiaoqing Fan
AU - Kangna Cao
AU - Xu Steven Xu
AU - Xiaoyu Yan
PY - 2026
DA - 2026/07/01
JO - BioData mining
DO - 10.1186/s13040-026-00589-3
UR - https://europepmc.org/article/MED/42902310
AB - Background Cancer cells frequently alter iron metabolism by increasing uptake or decreasing export, promoting oncogenesis and proliferation. However, the quantitative relationship between iron homeostasis and cancer remains underexplored.Methods and results We simplified these alterations into measurable changes in the expression levels of iron transport-related genes. We investigated the expression of iron transport-related genes by comparing genomic data of 478 human cancer cell lines to 105 normal tissue samples, as well as analyzing clinically paired 6903 tumor to 709 normal samples. We revealed that cancer cells exhibited increased expression of transferrin receptor 1 (TFR1) or CD44 for iron uptake and decreased expression of ferroportin for iron efflux to favor iron accumulation. Using machine learning, we identified TFR1, CD44, and ferroportin as the top three features consistently associated most with patient survival. We developed a cancer-specific iron risk score (CIRS) using parametric time-to-event models based on RNA-seq data from TFR1, CD44, and ferroportin in 4723 patients spanning 15 cancers. The CIRS, cross-validated in five external datasets, significantly stratified survival risk for various cancers, and predicted chemotherapy response in two independent breast cancer pharmacogenomic datasets.Conclusions Our study enhances the understanding of the relationship between iron homeostasis, survival, and chemotherapy response, laying the groundwork for iron-targeted therapies.
SN - 1756-0381
ER -