Circulating Hepcidin Levels Are an Independent Predictor of Survival in Microsatellite Stable Metastatic Colorectal Cancer Patient Candidates for Standard First-Line Treatment.

Background & Aim: Hepcidin, a key hormone in iron homeostasis, is synthesized by colorectal cancer (CRC) cells, particularly in the late stages of tumorigenesis. This study aimed to ascertain whether the serum levels of hepcidin could serve as a prognostic biomarker in microsatellite stable (MSS) metastatic CRC (mCRC). Specifically, we assessed the predictive value of baseline serum hepcidin levels for the overall survival (OS) of patients with MSS mCRC receiving first-line treatment with FOLFOX-panitumumab (RAS/BRAF wild-type) or FOLFOX-bevacizumab (RAS or BRAF mutations).

Methods: Serum samples were prospectively collected from 35 normal healthy volunteers (normal controls) and 55 patients with MSS mCRC and analyzed for their content of hepcidin by ELISA.

Results: Serum hepcidin levels were significantly greater in patients with mCRC than in the normal controls. In the mCRC group, patients with baseline levels of hepcidin greater than 40 ng/mL had a significantly shorter 1-year OS rate (39%) than those with hepcidin levels lower than 40 ng/mL (80%) [hazard ratio (HR): 2.94; 95% CI: 1.27-6.84; = 0.01]. A multivariate Cox regression analysis showed that the pre-treatment serum hepcidin levels were an independent prognostic factor for OS, not influenced by other well-known prognostic factors (i.e., CEA status, Karnofsky performance score, number of metastatic sites, RAS/BRAF mutations), and this was evident across all major patient subgroups.

Conclusions: Our data show that baseline serum levels of hepcidin are an independent risk factor for OS in MSS mCRC patients undergoing standard first-line treatment. Further prospective and extensive studies are needed to confirm and validate our findings.