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Published on: May 19, 2023
Detection of Ferritin Expression in Soft Tissue Sarcomas With MRI: Potential Implications for Iron Metabolic Therapy
Michael S Petronek1, Ann M Tomanek-Chalkley1, Varun Monga2
1Department of Radiation Oncology, Free Radical and Radiation Biology Program, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA.
Background:
Cancer cells often have altered iron metabolism relative to non-malignant cells with increased transferrin receptor and ferritin expression. Targeting iron regulatory proteins as part of a cancer therapy regimen is currently being investigated in various malignancies. Anti-cancer therapies that exploit the differences in iron metabolism between malignant and non-malignant cells (e.g. pharmacological ascorbate and iron chelation therapy) have shown promise in various cancers, including glioblastoma, lung, and pancreas cancers. Non-invasive techniques that probe tissue iron metabolism may provide valuable information for the personalization of iron-based cancer therapies. T2* mapping is a clinically available MRI technique that assesses tissue iron content in the heart and liver. We aimed to investigate the capacity of T2* mapping to detect iron stores in soft tissue sarcomas (STS).
Methods:
In this study, we evaluated T2* relaxation times ex vivo in five STS samples from subjects enrolled on a phase Ib/IIa clinical trial combining pharmacological ascorbate with neoadjuvant radiation therapy. Iron protein expression levels (ferritin, transferrin receptor, iron response protein 2) were evaluated by Western blot analysis. Bioinformatic data relating clinical outcomes in STS patients and iron protein expression levels were evaluated using the KMplotter database.
Results:
There was a high level of inter-subject variability in the expression of iron protein and T2* relaxation times. We identified that T2* relaxation time is capable of accurately detecting ferritin-heavy chain expression (r = -0.96) in these samples. Bioinformatic data acquired from the KMplot database revealed that transferrin receptor and iron-responsive protein 2 may be negative prognostic markers while ferritin expression may be a positive prognostic marker in the management of STS.
Conclusion:
These data suggest that targeting iron regulatory proteins may provide a therapeutic approach to enhance STS management. Additionally, T2* mapping has the potential to be used a clinically accessible, non-invasive marker of STS iron regulatory protein expression and influence cancer therapy decisions that warrants further investigation. Level of Evidence: IV.
Insights
Altered iron metabolism in cancer cells presents therapeutic opportunities. T2* mapping MRI can detect iron stores in soft tissue sarcomas (STS), correlating with ferritin levels and potentially guiding personalized cancer therapy decisions.
Area of Science:
- Oncology
- Radiology
- Biochemistry
Background:
- Cancer cells exhibit altered iron metabolism, with increased transferrin receptor and ferritin expression compared to normal cells.
- Targeting iron regulatory proteins is an emerging strategy in cancer therapy, showing promise in various malignancies.
- Non-invasive methods to assess tissue iron metabolism could personalize iron-based cancer treatments.
Purpose of the Study:
- To investigate the utility of T2* mapping, a clinical MRI technique, for detecting iron stores in soft tissue sarcomas (STS).
- To correlate T2* relaxation times with iron protein expression in STS samples.
- To explore the prognostic significance of iron-related proteins in STS patient outcomes.
Main Methods:
- Ex vivo evaluation of T2* relaxation times in five STS samples from a clinical trial combining pharmacological ascorbate and radiation therapy.
- Western blot analysis to quantify iron protein expression (ferritin, transferrin receptor, iron response protein 2).
- Bioinformatic analysis using the KMplotter database to assess the relationship between iron protein expression and clinical outcomes in STS.
Main Results:
- Significant inter-subject variability was observed in iron protein expression and T2* relaxation times.
- T2* relaxation time accurately detected ferritin-heavy chain expression (r = -0.96).
- Bioinformatic analysis indicated transferrin receptor and iron-responsive protein 2 as potential negative prognostic markers, while ferritin expression may be a positive prognostic marker in STS management.
Conclusions:
- Targeting iron regulatory proteins may offer a viable therapeutic approach to improve STS management.
- T2* mapping shows potential as a clinically accessible, non-invasive biomarker for STS iron regulatory protein expression.
- Further investigation is warranted to determine how T2* mapping can influence cancer therapy decisions in STS.
