Clinical Management Unit of Medical Oncology, Regional and Virgen de la Victoria University Hospitals-IBIMA BIONAND-CIMES-UMA Platform, 29010 Málaga, Spain.
Faculty of Medicine, University of Málaga, Andalucía Tech, Campus de Teatinos s/n, 29071 Málaga, Spain.
Int J Mol Sci. 2024 Jun 28;25(13):7091. doi: 10.3390/ijms25137091.
Breast cancer (BC) continues to pose a significant burden on global cancer-related morbidity and mortality, primarily driven by metastasis. However, the combined influence of microRNAs (miRNAs) and intratumoral microbiota on BC metastasis remains largely unexplored. In this study, we aimed to elucidate the interplay between intratumoral microbiota composition, miRNA expression profiles, and their collective influence on metastasis development in BC patients by employing 16S rRNA sequencing and qPCR methodologies. Our findings revealed an increase in the expression of miR-149-5p, miR-20b-5p, and miR-342-5p in metastatic breast cancer (Met-BC) patients. The Met-BC patients exhibited heightened microbial richness and diversity, primarily attributed to diverse pathogenic bacteria. Taxonomic analysis identified several pathogenic and pro-inflammatory species enriched in Met-BC, contrasting with non-metastatic breast cancer (NonMet-BC) patients, which displayed an enrichment in potential probiotic and anti-inflammatory species. Notably, we identified and verified a baseline prognostic signature for metastasis in BC patients, with its clinical relevance further validated by its impact on overall survival. In conclusion, the observed disparities in miRNA expression and species-level bacterial abundance suggest their involvement in BC progression. The development of a prognostic signature holds promise for metastasis risk assessment, paving the way for personalized interventions and improved clinical outcomes in BC patients.
乳腺癌(BC)仍然对全球癌症相关发病率和死亡率构成重大负担,主要由转移驱动。然而,miRNAs(miRNAs)和肿瘤内微生物群对 BC 转移的综合影响在很大程度上仍未得到探索。在这项研究中,我们旨在通过 16S rRNA 测序和 qPCR 方法阐明肿瘤内微生物群落组成、miRNA 表达谱及其对 BC 患者转移发展的综合影响。我们的研究结果显示,转移性乳腺癌(Met-BC)患者的 miR-149-5p、miR-20b-5p 和 miR-342-5p 的表达增加。Met-BC 患者表现出微生物丰富度和多样性的增加,主要归因于多种致病性细菌。分类分析鉴定出几种在 Met-BC 中富集的致病性和促炎物种,与非转移性乳腺癌(NonMet-BC)患者形成对比,后者显示出潜在益生菌和抗炎物种的富集。值得注意的是,我们确定并验证了 BC 患者转移的基线预后特征,其对总生存的影响进一步验证了其临床相关性。总之,观察到的 miRNA 表达和物种水平细菌丰度的差异表明它们参与了 BC 的进展。预后特征的开发有望用于转移风险评估,为 BC 患者的个性化干预和改善临床结果铺平道路。