Analyzing the drivers of cancer relapse: hypocalcemia and iron absorption in hormone-dependent female cancers

Am J Transl Res. 2022 Sep 15;14(9):6563-6573. eCollection 2022.

Abstract

Background: Alterations in the levels of nutrients like calcium, ferritin, and electrolytes play a pivotal role in human physiology and might serve as biomarkers. Ferritin, an iron storage protein is important in various metabolic reactions of both cancer and cancer stem cells (CSCs) and is found to regulate 'stemness' leading to cancer relapse. Interestingly, ferritin levels are found to be regulated by calcium uptake. Several studies have shown that high levels of calcium inhibit absorption of iron, thereby reducing ferritin levels. In the present study, we evaluated and correlated the serum ferritin and calcium levels in pre- and post-treated hormone-dependent female cancers and deciphered their role in tumor recurrence and relapse.

Materials and methods: The present retrospective study was approved by the Institutional Ethical Committees (IEC) of GIMSR (No. GIMSR/Admn./Ethics/approval/IEC-3/2021), and Omega cancer hospitals (Reg No: ECR/1486/Inst/AP/2020). Serum from 197 clinical samples diagnosed with breast, cervical, and ovarian cancers (99 pre-and 98 post-treatment) and 10 blood samples were analyzed for ferritin and calcium using auto bioanalyzer and sandwich enzyme-linked immunosorbent assay (ELISA).

Results: Ferritin levels were elevated in both pre- and post-treatment hormone-dependent female cancer patients while calcium levels showed gradual decrease. The mean ferritin value for pre-treatment was 0.0409 mg/dL while it was 0.0428 mg/dL for post-treatment hormone-dependent female cancer.

Conclusion: Our results suggest that hypocalcaemia in post-treatment cancer patients leads to ferritin accumulation which might make these patients more prone to tumor recurrence and relapse.

Keywords: Cancer relapse; calcium; cancer stem cells; estrogen; serum ferritin; stemness.