Serum ferritin as a non-invasive prognostic biomarker in cancer: a systematic review and meta-analysis

Abstract

Purpose Serum ferritin (SF) is a routine biomarker reflecting iron status and systemic inflammation. We performed a systematic review and meta-analysis to validate the prognostic value of circulating SF for overall survival (OS) in adult patients with malignant tumors. Experimental design We searched PubMed, Embase, Cochrane Library, the Chinese databases CNKI and Wanfang from inception to December 31, 2025, for retrospective cohort studies reporting the association between SF levels and overall survival (OS) in cancer patients. Two reviewers independently screened studies, extracted data, and assessed quality via the Newcastle-Ottawa Scale (NOS). Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated, with prespecified subgroup, sensitivity, and publication bias analyses. This study was prospectively registered in PROSPERO (CRD420251271950). Results Ten moderate-to-high quality studies (3,083 patients) were included. Elevated SF was significantly associated with increased mortality risk (pooled HR = 1.78, 95% CI: 1.55–2.05, P < 0.001), with consistent effects across all prespecified subgroups (all P for interaction > 0.05). We preliminarily identified a 300–500 ng/mL SF threshold as the high-risk range for adverse outcomes (exploratory analysis, 2 studies, HR = 2.26). Publication bias adjustment did not alter the core conclusion (adjusted HR = 1.70). Conclusion Higher SF correlates with worse OS in adult patients with both hematologic malignancies and solid tumors. Our data only offers preliminary reference for risk stratification, and we cannot recommend routine clinical application right now. Larger prospective trials are needed to verify the ferritin concentration cut-off and different predictive values of pre- and post-treatment testing. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420251271950.