Molecular mechanisms of bone metastasis in breast cancer based on transcriptomic and microbiomic analysis

Bone metastasis (BM) in breast cancer affects patient prognosis, but its molecular mechanisms and relationship with the gut microbiome are not well understood. This study aims to explore gene expression and gut microbiome differences between BM and non-bone metastasis (BNM) patients, which could shed light on cancer progression and metastasis.

We utilized a multi-omics approach, integrating transcriptomic and microbiomic data. Bioinformatics techniques including differential expression analysis, functional enrichment, protein-protein interaction network analysis, and LDA effect size analysis were applied. We also constructed miRNA regulatory networks and gene-gene interaction networks to identify key genes and microbial functions involved in BM.

The analysis identified significant upregulation of genes such as IBSP, PROM1, and IDO1 in BM patients. miRNA analysis suggested that let-7 family members might regulate these genes and influence cancer progression. Gene-gene network analysis revealed a synergistic role for genes like THBS1 and ITGB3 in tumor progression. Regarding the gut microbiome, BM patients exhibited enriched pathways related to arachidonic acid metabolism, steroid hormone synthesis, and thyroid hormone synthesis, potentially impacting immunity and metabolism. Additionally, Human papillomavirus (HPV) infection pathways were significantly enriched, indicating a possible role in BM.

The study highlights distinct gene expression and gut microbiome differences between BM and BNM patients. HPV infection may play a crucial role in BM development, offering new potential biomarkers and therapeutic targets for early diagnosis and treatment of BM in breast cancer.