Predictive value of serum biomarkers for survival in melanoma: a systematic review and meta-analysis

Abstract

Abstract Malignant melanoma is responsible for most skin cancer–related deaths due to its unpredictable behavior. Serum biomarkers have been widely investigated to improve prognostic assessment, yet their clinical utility remains inconclusive. This systematic review and meta-analysis evaluated the prognostic significance of serum biomarkers in melanoma. Following PRISMA guidelines and a registered protocol (PROSPERO: CRD42023486532), PubMed, EMBASE, and CENTRAL were searched for studies assessing biomarkers and survival outcomes. Univariate analyses revealed that elevated levels of LDH (HR 2.29, 95%-CI:1.97–2.67), S100B (HR 2.52, 95%-CI:1.59–3.99), circulating tumor DNA (ctDNA) (HR 2.61, 95%-CI:1.90–3.58), neutrophil-to-lymphocyte ratio (NLR) (HR 2.34, 95%-CI:1.86–2.93), and interleukin-6 (HR 3.11, 95%-CI:2.44–3.96) were significantly associated with reduced overall survival. Similarly, higher levels of LDH (HR 2.04, 95%-CI:1.68–2.47), S100B (HR 1.94, 95%-CI:1.39–2.70), ctDNA (HR 2.57, 95%-CI:1.95–3.39), and NLR (HR 2.38, 95%-CI:1.52–3.73) predicted shorter progression-free survival. These associations persisted in multivariable-adjusted analyses for LDH, ctDNA, NLR, IL-6, S100B, and CRP supporting their predictive relevance. LDH remains a reliable and cost-effective biomarker, while NLR may provide complementary prognostic information in patients receiving immune checkpoint inhibitors. Emerging biomarkers such as ctDNA demonstrate promising prognostic potential, but further evaluation is required before routine clinical implementation.