Oncofetal chondroitin sulfate positive circulating tumor cells as prognostic biomarkers in early-stage melanoma

Progression occurs in more than 10% of melanoma patients initially diagnosed with local disease, emphasizing the need for improved risk stratification even in early stages. In this study, we used an enrichment method based on recombinant Plasmodium falciparum VAR2CSA protein to enable the capture of rare circulating tumor cells (CTCs) from a single blood draw in early-stage (AJCC I-II) melanoma patients. CTCs were subsequently identified using fluorescent antibodies targeting tumor initiating and melanoma specific cell markers. In parallel, we investigated circulating tumor DNA (ctDNA) in these patients. Among 92 early-stage melanoma patients, CTCs were detected in 21 patients (22.8%) at time of initial diagnosis. The presence of CTCs was significantly associated with an unfavorable clinical outcome, such as disease progression or death related to melanoma disease, with a median observation time of 30 months (IQR 24.0-36.0) (p = 0.043). Furthermore, when combining CTC with ctDNA detection, a highly significant correlation with disease progression was observed (p = 0.014) underlining the role of early tumor cell dissemination in melanoma disease. These findings suggest that CTC assessment, particularly when combined with ctDNA analysis, may represent a valuable biomarker to facilitate risk stratification of early-stage melanoma patients to improve personalized treatment approaches.