Transferrin Receptor 1 (TFRC) and Ferroptosis-Related Biomarkers in Oncology: Analytical Evaluation and Translational...

One of the important regulators of cellular iron uptake is transferrin receptor 1 (TFRC), which is closely linked to ferroptosis, an iron-dependent form of regulated cell death caused by lipid peroxidation. TFRC and ferroptosis-related biomarkers (including soluble transferrin receptor, labile iron pools, 4-hydroxynonenal, malondialdehyde, glutathione status, GPX4 expression, and oxidized species of phospholipids) can be measured in tissue, blood, and single-cell systems and are beginning to emerge as potential biomarkers in laboratory medicine in oncology. This review considers their analytical and translational applications in human malignancies, focusing on clinical chemistry, diagnostic laboratory medicine, and precision oncology. We combined data showing a relationship between TFRC expression and ferroptosis-related signatures to classify diseases, explore reported associations with prognosis, treatment response, and survival. We also considered their possible uses in stratifying risks, therapies, pharmacodynamic aspects, and longitudinal disease assessment. Emphasis is placed on laboratory variables that influence implementation, such as the selection of matrix specimens, variation in preanalytical factors, assay standardization, platform-dependent cutoff values, calibrations, and cross-platform validation. The review also discusses how digital pathology, artificial intelligence, machine learning, and multimarker analytical frameworks may support biomarker quantification and interpretation after appropriate validation. Overall, a validated analytical workflow, standardized reporting, inter-laboratory harmonization, and prospective clinical validation are required to support the clinical translation of TFRC-ferroptosis biomarker panel tests. This review offers a laboratory medicine-centered framework for understanding the potential and current limitations of TFRC and ferroptosis-related biomarkers as analytical targets in precision oncology.