The intratumoral microbiome is negatively associated with malignancy in dermatofibrosarcoma protuberans

In recent years, growing evidence demonstrated the critical roles of intratumoral microbes in tumors. However, the characteristics of intratumoral microbiome in dermatofibrosarcoma protuberans (DFSP) and their associations with tumor malignancy remains unexplored. Here, 106 whole-genome sequencing (WGS) data of the paired biopsy and blood samples from 53 DFSP patients were utilized, in which we extracted high-quality non-human reads to assign microbial taxonomic annotation by Kraken2 and PlusPF database. Meanwhile, significantly elevated non-human reads, microbial abundance, and bacterial load were detected in tumor compared to blood samples. To minimize the impact of contaminants and noise, we conducted a series of filtering procedures and treated blood samples as negative controls. Notably, we found that over 98% of intratumor microbes belonged to bacteria, and that the dominant taxa and alpha-diversity of intratumoral bacteria all exhibited significantly negative correlations with Ki67 expression in tumors. Specifically, the 84 key intratumoral species were identified to be associated with the reduced tumor malignancy, as evidenced by the diminished Ki67 expression, decreased tumor volume, and fewer COL1A1-PDGFB fusion events. These findings highlighted the tumor-suppressive potential of intratumoral microbiome, thereby providing a novel insight into DFSP pathogenesis and clinical management. IMPORTANCETo our knowledge, this is the first study to explore the intratumoral microbiome in DFSP. Microbial DNA signatures could be detected by whole-genome sequencing (WGS) and enabled a comprehensive view of the microbial landscape, thus we analyzed 106 WGS data of the paired biopsy and blood samples from 53 DFSP patients. Our analysis revealed that the dominant taxa and alpha-diversity of intratumoral microbiome all showed significantly negative correlations with Ki67 expression of tumor samples. This study indicated the tumor-suppressive role of intratumoral microbiome in DFSP and highlighted the potential clinical significance in understanding DFSP pathogenesis and guiding therapeutic management strategies.