Circulating Calprotectin Distinguishes Metastatic Melanoma and Predicts Liver Metastasis

Calprotectin, a heterodimer of the S100A8 and S100A9 proteins, has been implicated in cancer-related inflammation and metastasis. Its role in melanoma progression, particularly in organ-specific metastasis, remains underexplored. In this retrospective study, plasma calprotectin levels were measured in 201 individuals, including healthy controls (<i>n</i> = 22), melanoma patients without evidence of metastasis (<i>n</i> = 71), and patients with metastatic melanoma (<i>n</i> = 108). Calprotectin concentrations were determined using the ELISA assay. Receiver operating characteristic (ROC) curve analyses were used to evaluate its diagnostic value, both alone and in combination with established biomarkers S100B and LDH. Plasma calprotectin levels were significantly elevated in patients with metastatic melanoma compared to non-metastatic patients (<i>p</i> < 0.001). Calprotectin showed moderate diagnostic value (AUC = 0.672), which improved to 0.755 when combined with S100B and LDH. Organ-specific analysis revealed that patients with liver metastases exhibited the highest calprotectin concentrations, with good discriminatory power (AUC = 0.710). No significant association was found between calprotectin levels and the type of metastasis identified (lymphatic vs. hematogenous). Logistic regression analysis showed that calprotectin levels above 2728 ng/mL were associated with a 7.4-fold increased risk of liver metastasis. Calprotectin is a promising blood-based biomarker that may enhance the detection of metastatic melanoma, particularly in cases with liver involvement. These findings suggest that calprotectin could be integrated into multivariable prediction models to improve risk stratification in clinical practice.