Regulation of hepcidin through GDF-15 in cancer-related anemia

Clin Chim Acta. 2014 Jan 20:428:14-9. doi: 10.1016/j.cca.2013.10.015. Epub 2013 Oct 25.

Abstract

Background: High prevalence and unresponsiveness to erythropoiesis-stimulating agents are 2 major limitations to the treatment of cancer-related anemia (CRA). They are often related to the dis-regulation of iron metabolism regulated by hepcidin, but the regulatory pathway of hepcidin in CRA is poorly understood. Enhanced GDF-15 levels contribute to the cancer progression and metastasis, and also have been found to suppress hepcidin expression in anemia characterized by ineffective erythropoiesis. The pathophysiological mechanisms and the relationship of GDF-15 and hepcidin in CRA remain to be elucidated.

Methods: The concentrations of hepcidin and GDF-15 as well as the hematological and the iron parameters were determined in sera from 131 patients with cancer and 40 healthy controls.

Results: Serum GDF-15 levels were increased significantly in patients with the severe CRA, compared with the mild or no CRA patients and the controls. Increasing GDF-15 levels corresponded to decreasing hepcidin concentrations. A trend toward a correlation between high levels of GDF-15 and poor prognosis of cancer was also found. Elevation of GDF-15 concentrations suppressed hepcidin expression at high concentrations.

Conclusions: Our findings suggest that tumor progression results in increased GDF-15 secretion, which may down-regulate hepcidin expression, resulting in iron overload in cancer patients; this phenomenon has also been found in some patients with sideropenic anemia due to chronic blood loss.

Keywords: ACD; AJCC; American Joint Commission for Cancer Staging; CDAI; CRA; EC; FID; GC; GDF-15; Hepcidin; IDA; IGF-I; IUCC; International Union Against Cancer; Iron; PTGF-β; RC; RET; STAT-3; TGF-β; anemia of chronic disease; cancer-related anemia; congenital dyserythropoietic anemia-I; esophageal cancer; functional iron deficiency; gastric cancer; growth differentiation factor 15; insulin-like growth factor I; iron-deficiency anemia; placental transforming growth factor-β; rectal cancer; reticulocyte count; signal transducer and activator of transcription-3; transforming growth factor-β.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia / blood
  • Anemia / diagnosis
  • Anemia / metabolism*
  • Female
  • Gastrointestinal Neoplasms / blood
  • Gastrointestinal Neoplasms / diagnosis
  • Gastrointestinal Neoplasms / metabolism*
  • Growth Differentiation Factor 15 / blood
  • Growth Differentiation Factor 15 / metabolism*
  • Hepcidins / blood
  • Hepcidins / metabolism*
  • Humans
  • Male
  • Middle Aged

Substances

  • GDF15 protein, human
  • Growth Differentiation Factor 15
  • Hepcidins