What Cancers Cause Elevated Ferritin Levels?

Ferritin is a protein that stores and releases iron in the body, playing a crucial role in maintaining iron balance. Elevated levels can result from infections, inflammatory diseases, and certain cancers. In malignancies, high ferritin may indicate tumor activity, increased inflammation, or disruptions in iron metabolism, making it a potential diagnostic and prognostic marker.

Ferritin And Cancer Physiology

Ferritin regulates iron availability for metabolic processes while preventing oxidative damage. In cancer, levels often rise due to altered iron metabolism, tumor-driven inflammation, and increased cellular turnover. Malignant cells require more iron for rapid proliferation, leading to upregulated ferritin synthesis. This dependency is particularly evident in aggressive tumors, where ferritin supports growth and shields cancer cells from oxidative stress-induced apoptosis.

Tumor cells manipulate iron regulatory proteins, such as transferrin receptors and ferroportin, to enhance iron uptake while limiting its export. This imbalance results in intracellular iron accumulation, stimulating ferritin production. Research in Cancer Research highlights ferritin’s role in immune evasion and therapy resistance, making it a potential prognostic biomarker.

Ferritin also influences cancer cell survival through ferroptosis, an iron-dependent form of cell death. While ferroptosis can suppress tumors, many cancers resist it by increasing ferritin expression, reducing free iron availability, and preventing lipid peroxidation. Studies in Nature Reviews Cancer suggest targeting ferritin-mediated iron storage could improve ferroptosis-inducing therapies.

Hematologic Malignancies

Blood cancers, including leukemias, lymphomas, and multiple myeloma, frequently elevate ferritin levels due to disrupted iron metabolism and systemic inflammation. These malignancies increase cellular turnover and iron sequestration within macrophages, with ferritin rising as an acute-phase reactant.

Acute myeloid leukemia (AML) shows a strong correlation between ferritin elevation and disease activity. AML cells rapidly proliferate, increasing intracellular iron storage. Studies in Blood Advances indicate that AML patients with high ferritin levels often experience more aggressive disease and poorer survival, as iron fuels leukemic cell proliferation and supports oxidative stress defenses.

Lymphomas, particularly diffuse large B-cell lymphoma (DLBCL), also contribute to abnormal ferritin levels through chronic inflammation and cytokine-driven iron sequestration. Research in The Lancet Haematology links high serum ferritin at diagnosis to lower response rates to immunochemotherapy, reflecting its association with tumor burden and progression.

Multiple myeloma disrupts iron homeostasis through inflammatory cytokines like interleukin-6 (IL-6), which drives ferritin synthesis. Elevated ferritin correlates with higher tumor burden and poorer prognosis. A meta-analysis in Haematologica found that patients with ferritin levels above 700 ng/mL had significantly reduced progression-free survival.

Hepatic And Pancreatic Tumors

Liver and pancreatic cancers frequently disrupt iron metabolism, leading to elevated ferritin levels. Hepatocellular carcinoma (HCC), the most common primary liver cancer, often arises in the setting of chronic liver disease, where iron overload contributes to tumor progression. Excess iron in hepatocytes, whether from hereditary hemochromatosis, chronic hepatitis, or fatty liver disease, promotes oxidative stress and DNA damage, facilitating carcinogenesis.

Pancreatic ductal adenocarcinoma (PDAC) also alters iron homeostasis. PDAC cells upregulate ferritin synthesis to sustain rapid proliferation while mitigating oxidative stress. A retrospective analysis in Pancreatology found that patients with ferritin levels above 600 ng/mL were more likely to have metastatic disease at diagnosis, emphasizing ferritin’s prognostic value.

Both HCC and PDAC induce systemic inflammation, amplifying ferritin production. Chronic inflammatory states, such as liver cirrhosis or pancreatitis, lead to persistent iron sequestration within macrophages, contributing to elevated circulating ferritin. Tumor-induced alterations in hepcidin expression further exacerbate iron retention, fostering an environment that supports malignancy.

Breast And Prostate Cancers

Ferritin levels in breast and prostate cancers reflect the link between tumor metabolism and iron regulation. Both malignancies rely on iron for rapid proliferation, with ferritin playing a crucial role in modulating this demand.

In breast cancer, particularly aggressive subtypes like triple-negative breast cancer (TNBC), ferritin is frequently upregulated due to increased iron uptake and storage. Research shows breast cancer cells manipulate iron transport proteins to enhance intracellular iron availability, fueling tumor progression. Elevated ferritin has been associated with higher tumor grades and poorer prognoses.

Prostate cancer exhibits similar iron-related metabolic changes, with ferritin rising alongside tumor burden. Advanced and castration-resistant prostate cancers (CRPC) disrupt iron homeostasis to maximize retention for sustained proliferation. Studies suggest ferritin expression in prostate tumors contributes to treatment resistance, particularly in patients undergoing androgen deprivation therapy.

Other Cancer Types

Lung cancer, particularly small cell lung carcinoma (SCLC), frequently presents with abnormal iron metabolism, leading to elevated ferritin concentrations. SCLC’s rapid proliferation necessitates enhanced iron sequestration, resulting in ferritin overexpression. A study in Lung Cancer found that patients with extensive-stage SCLC had significantly higher serum ferritin levels, suggesting its role as a biomarker for tumor burden and therapeutic response.

Gastrointestinal cancers, such as colorectal and gastric malignancies, also demonstrate ferritin dysregulation due to chronic inflammation and altered iron absorption. Colorectal tumors manipulate iron regulatory proteins to facilitate intracellular iron accumulation, fostering malignant progression. Gastric cancer, often linked to chronic Helicobacter pylori infection, exhibits persistent inflammation that drives ferritin synthesis. Research in Gastroenterology indicates that metastatic colorectal cancer patients with ferritin levels above 500 ng/mL had significantly shorter progression-free survival, reinforcing ferritin’s role as both a tumor marker and a mediator of disease aggressiveness.