Zhang Dihui, Long Manli, Meng Lingcui, Li Yongjin, Chen Bolai, Lin Dingkun, Su Guoyi
Orthopedics department, Guangdong Provincial Hospital of Chinese Medicine (The Second Affiliated Hospital of Guangzhou University of Chinese Medicine), Guangzhou, China.
Guangzhou Orthopedics Hospital, Guangzhou, China.
Cancer Causes Control. 2025 Sep 5. doi: 10.1007/s10552-025-02057-5.
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.
乳腺癌骨转移（BM）影响患者预后，但其分子机制以及与肠道微生物群的关系尚不清楚。本研究旨在探索BM患者与非骨转移（BNM）患者之间的基因表达和肠道微生物群差异，这可能有助于揭示癌症进展和转移情况。
我们采用多组学方法，整合转录组学和微生物组学数据。应用了包括差异表达分析、功能富集、蛋白质-蛋白质相互作用网络分析和LDA效应大小分析等生物信息学技术。我们还构建了miRNA调控网络和基因-基因相互作用网络，以识别参与BM的关键基因和微生物功能。
分析发现BM患者中IBSP、PROM1和IDO1等基因显著上调。miRNA分析表明，let-7家族成员可能调控这些基因并影响癌症进展。基因-基因网络分析揭示了THBS1和ITGB3等基因在肿瘤进展中的协同作用。关于肠道微生物群，BM患者表现出与花生四烯酸代谢、类固醇激素合成和甲状腺激素合成相关的富集通路，可能影响免疫和代谢。此外，人乳头瘤病毒（HPV）感染通路显著富集，表明其在BM中可能发挥作用。
该研究突出了BM患者与BNM患者之间不同的基因表达和肠道微生物群差异。HPV感染可能在BM发展中起关键作用，为乳腺癌BM的早期诊断和治疗提供了新的潜在生物标志物和治疗靶点。
