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. 2025 Apr 21;16(8):2421-2433.
doi: 10.7150/jca.102131. eCollection 2025.

Pair-matched analysis of Circulating Melanoma Cells (CMCs) before and after Immunotherapy in Relation to other Melanoma-Specific Biomarkers

Paula Sawerska  1   2 , Aneta Konwerska  1 , Łukasz Galus  3 , Agata Kolecka-Bednarczyk  4 , Karolina Buszka  1   2 , Damian Rusek  5 , Agnieszka Seraszek-Jaros  6 , Michał Nowicki  1 , Jacek Mackiewicz  3 , Joanna Budna-Tukan  1   4   7
Affiliations

Pair-matched analysis of Circulating Melanoma Cells (CMCs) before and after Immunotherapy in Relation to other Melanoma-Specific Biomarkers

Paula Sawerska et al. J Cancer. .

Abstract

Melanoma remains challenging in terms of diagnosis and treatment, and there is an urgent need to implement accurate diagnostic methods and personalized treatment to improve clinical outcomes. Therefore, it may be useful to enrich the panel of melanoma markers already in use and develop combinations of biomarkers for disease prognosis and monitoring. Data suggest that a promising biomarker for such a combination is circulating melanoma cells (CMCs). Although the relevances of various biomarkers in diagnosis, prognosis and treatment monitoring in melanoma have been extensively studied, we aimed at comprehensive investigation and comparison of liquid biopsy and tissue biomarkers with clinical status of the patient. Specifically, we focused on CMCs, by comparing the number of CMCs, including pre- and post-treatment. Furthermore, we have assessed the expression of the PMEL and Melan-A markers and the S100B and TIMP-1 protein levels in representative blood samples from melanoma patients and healthy controls. The number of CMCs in the study group was significantly higher than in the CMC-negative control group. However, there was no significant difference between the incidence of CMCs in the pre- and post-treatment blood draws. Nonetheless, we have observed a negative correlation between LDH levels and PFS, and a negative correlation between S100B levels and lymphocyte counts. The results of the study indicate that combinations of biomarkers, rather than any single biomarker alone, possess the highest clinical application potential, which urges further research on larger patient groups.

Keywords: CMCs; biomarkers; immunotherapy; liquid biopsy; melanoma.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
Distribution of detected circulating melanoma cells (CMCs) using the CellSearch® system tested separately before and after implemented therapy. Presented results of CMC enumeration show performance of technology in: A) melanoma patients before the treatment, B) melanoma patients after the treatment and C) control group of healthy individuals.
Figure 2
Figure 2
Representative images of CMCs detected in melanoma patients using the CellSearch® system. Enriched and stained cells were identified as tumor cells according to the following criteria: HMW-MAA-positive, DAPI-positive, CD45-negative, and negative for the last channel.
Figure 3
Figure 3
Circulating melanoma cells (CMCs) detection rate before and after treatment reflecting the effectivity of the implemented therapy. Matched-pair analysis of CMCs enumerated with the CellSearch® system: A) comparison of CMC counts in melanoma patients before and after the treatment, B) changes in CMC counts before vs. after the treatment.
Figure 4
Figure 4
Representative images of immunohistochemical staining: A) positive PMEL expression, B) positive Melan-A expression and C) negative staining control.
Figure 5
Figure 5
Bar graph illustrating significant differences in S100B concentration in serum between melanoma patient group and control group of healthy individuals.
Figure 6
Figure 6
Correlation between parameters including: S100B serum concentration, LDH serum concentration, PFS, OS and lymphocyte count.
See this image and copyright information in PMC

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