Iron biomarkers for prognosis, diagnosis, and therapeutic insight in colorectal cancer

Background Colorectal cancer (CRC) is a significant global health concern. It ranks as the third most common cancer, accounting for about 10% of all cancer cases, with projections estimating a substantial increase in this burden, reaching 3.2 million new cases and 1.6 million deaths annually by 2040. Although current CRC biomarkers can be helpful, each has limitations. CEA is used to monitor patients after surgery and detect recurrence, but it is not widely employed for early detection or diagnosis at the initial stages. Although the blood test for mSEPT9 is convenient and non-invasive, it tends to perform better than CEA in advanced disease stages. Moreover, CA19–9 is not specific to CRC but can still provide prognostic clues, with higher levels often indicating poorer outcomes. Stool tumor M2-PK appears useful for early detection, although it is not yet widely used and lacks standardized protocols. Aim There is a clear need for new, reliable, and affordable biomarkers to improve early detection and guide patient care more effectively. The literature indicates limitations in classifying the diagnostic and prognostic performance of iron biomarkers compared with conventional panels. Additionally, there is a gap in understanding the mechanisms underlying ferroptosis and their relationship to patient outcomes. Addressing these gaps, this paper evaluates whether iron-related biomarkers can complement current CRC markers for diagnosis and prognosis. Scientific concepts of the review Iron dysregulation plays a central role in how CRC develops and progresses. When hepcidin breaks down ferroportin, when IRP2 suppresses ferritin, and when NUBP2 alters iron sulfur metabolism along with the overexpression of TfR1, these processes collectively increase the iron labile pool. This excess iron fuels tumor growth and affects the sensitivity of cancer cells to ferroptosis. Because these biomarkers can be measured in tissue, they are valuable for diagnostic purposes and treatment planning.