Ferroptosis biomarkers, a potential diagnosis in colorectal cancer

Colorectal cancer (CRC) is a major health concern with increasing incidence, which its early diagnosis, plays a vital role in the success rate of its treatment. Recent investigations have revealed that ferroptosis, a newly discovered type of non-apoptotic and iron-dependent cell death, significantly contributes to the development and progression of various cancers, particularly CRC. The process of this cell death is exacerbated by Iron Overload, which facilitate the Fenton reaction, ultimately leading to an increase in reactive oxygen species (ROS) that induce lipid peroxidation and result in cellular damage. Also, numerous biomarkers associated with ferroptosis have been discovered, which can serve as valuable tools in the diagnosis and prognosis of CRC. Glutathione Peroxidase ۴ (GPX۴) is a key regulator of ferroptosis prevents lipid peroxidation. Reduced GPX۴ expression is linked to heightened ferroptosis in colorectal cells, suggesting its potential as a biomarker for cancer prediction in this context. Other ferroptosis biomarkers, like Acyl-CoA Synthetase Long-Chain Family Member ۴ (ACSL۴), that involved in synthesizing fatty acids for lipid peroxidation during ferroptosis, and Malondialdehyde (MDA) and ۴-HNE, byproducts of lipid peroxidation, are key indicators of ferroptosis and could be used to diagnose CRC. Additionally, certain genes that are crucial for the regulation of ferroptosis, such as SLC۷A۱۱, TP۵۳, and NRF۲, have been found to be associated with the prognosis of CRC. Also, ferroptosis-related genes such as CYP۱B۱, FSP-۱, NCOA۴, and various non-coding RNAs are increasingly recognized for their roles in colorectal cancer. Their expression levels can significantly influence tumor behavior, treatment responses, and the potential for ferroptosis as a therapeutic strategy. Furthermore, Embryonic Lethal Abnormal Vision Like ۱ (ELAVL۱), an RNA-binding protein, is involved in regulating mRNA stability and translation linked to ferroptosis. Its expression is changed in CRC tissues compared to healthy tissues, indicating its potential as a biomarker for CRC progression, and High Mobility Group Box ۱ (HMGB۱) is a protein linked to inflammation, cell death, and ferroptosis. Its levels in CRC patients may impact tumor progression and outcomes. In summary, ferroptosis is an emerging target for cancer diagnosis and treatment and can have complex roles, influencing both tumor suppression and progression. Further research is needed to optimize ferroptosis biomarkers-based diagnosis and evaluate their clinical potential. In this review, we aim to introduce ferroptosis cell death and its critical pathway in initiate and progress of colorectal cancer and the role of its biomarkers in the diagnosis of CRC.

کلیدواژه ها:

Colorectal Cancer ، Ferroptosis Cell Death ، Colorectal Molecular Diagnosis ، Ferroptosis Biomarkers