The TOPOSCORE microbiome index as a potential marker of response to neoadjuvant monotherapy in patients with cutaneous melanoma

<jats:p> <jats:bold>Introduction.</jats:bold> Immune checkpoint inhibitors have substantially improved outcomes in a subset of patients with melanoma. Нowever, clinical responses remain heterogeneous. The gut microbiota is considered a promising source of biomarkers of immunotherapy response, but the reproducibility of proposed microbiome-based indices in independent clinical cohorts requires further validation. </jats:p> <jats:p> <jats:bold>Aim.</jats:bold> To evaluate the applicability of the TOPOSCORE microbiome index in a clinical cohort of patients with melanoma and to analyze its association with major pathomorphological response (MPR), as well as with event-free survival (EFS) and overall survival (OS). </jats:p> <jats:p> <jats:bold>Mat</jats:bold> <jats:bold>erials</jats:bold> <jats:bold/> <jats:bold>and мethods.</jats:bold> We analyzed patients with melanoma for whom shotgun metagenomic sequencing data of gut microbiota samples and clinical treatment response data were available. Taxonomic profiling was performed using MetaPhlAn 4, followed by calculation of the TOPOSCORE index. We assessed the association of the TOPOSCORE binary classification (SIG1+/ SIG2+), its components (SIG1_count, SIG2_count, S_score), and derived metrics with MPR, as well as with EFS and OS. We applied Fisher’s exact test, the Mann – Whitney U test, Kaplan–Meier survival analysis, and the log-rank test. </jats:p> <jats:p> <jats:bold>Results.</jats:bold> Binary classification of TOPOSCORE showed no association with MPR: the frequency of MPR+ was comparable in the SIG1+ and SIG2+ groups (Fisher’s exact test, OR = 0.99; p = 1.0). The TOPOSCORE components (SIG1_count, SIG2_count, S_score) also did not differ between the MPR+ and MPRgroups. Survival analysis did not reveal statistically significant differences in EFS and OS when stratified by TOPOSCORE, whereas MPR demonstrated a stronger association with outcomes, including EFS (log-rank p &lt; 0.001) and OS (log-rank p = 0.036). </jats:p> <jats:p> <jats:bold>Conclusion.</jats:bold> In the clinical cohort of melanoma patients studied, TOPOSCORE showed no association with MPR, EFS, or OS, nor did it demonstrate predictive value for morphological response. The data obtained suggest that TOPOSCORE can be considered a potential, but as yet unvalidated, microbiome marker that requires further testing in larger independent cohorts. </jats:p>