背景:乳腺癌(BC)患者容易发生远处转移,尤其是骨转移。
方法:所有基于开放访问数据的分析均在R软件中进行,依赖于多个算法和软件包。使用定量实时PCR作为检测RNA水平的方法来检测特定基因的RNA水平。为了评估BC细胞的增殖能力,我们利用CCK8测试,菌落形成,和5-乙炔基-20-脱氧尿苷测定。通过使用Transwell测定和伤口愈合测定评价BC细胞的侵袭和迁移。
结果:在我们的研究中,我们根据来自多个BC队列的数据确定了与BC骨转移有关的分子.然后,我们全面研究了这些分子的作用模式和潜在的生物学作用。我们发现在鉴定的分子中,EMP1,ACKR3,ITGA10,MMP13,COL11A1和THY1与患者预后显着相关,并且主要在CAF中表达。因此,我们探索了BC微环境中的CAF。结果表明,CAFs可以激活多种致癌途径,其中大多数途径在癌症转移中起重要作用。同时,我们注意到CAFs和恶性之间的相互作用,内皮,和M2巨噬细胞。此外,我们发现CAFs可以诱导BC微环境的重塑,促进BC细胞的恶性行为。然后,我们鉴定了MMP13用于进一步分析.发现MMP13可以增强BC细胞的恶性表型。同时,进行了生物富集和免疫浸润分析,以显示MMP13在BC中的作用模式。
结论:我们的结果可以提高研究人员对BC骨转移的潜在机制的理解。
BACKGROUND: Breast cancer (BC) patients tend to suffer from distant metastasis, especially bone metastasis.
METHODS: All the analysis based on open-accessed data was performed in R software, dependent on multiple algorithms and packages. The RNA levels of specific genes were detected using quantitative Real-time PCR as a method of detecting the RNA levels. To assess the ability of BC cells to proliferate, we utilized the CCK8 test, colony formation, and the 5-Ethynyl-20-deoxyuridine assay. BC cells were evaluated for invasion and migration by using Transwell assays and wound healing assays.
RESULTS: In our study, we identified the molecules involved in BC bone metastasis based on the data from multiple BC cohorts. Then, we comprehensively investigated the effect pattern and underlying biological role of these molecules. We found that in the identified molecules, the EMP1, ACKR3, ITGA10,
MMP13, COL11A1, and THY1 were significantly correlated with patient prognosis and mainly expressed in CAFs. Therefore, we explored the CAFs in the BC microenvironment. Results showed that CAFs could activate multiple carcinogenic pathways and most of these pathways play an important role in cancer metastasis. Meanwhile, we noticed the interaction between CAFs and malignant, endothelial, and M2 macrophage cells. Moreover, we found that CAFs could induce the remodeling of the BC microenvironment and promote the malignant behavior of BC cells. Then, we identified
MMP13 for further analysis. It was found that
MMP13 can enhance the malignant phenotype of BC cells. Meanwhile, biological enrichment and immune infiltration analysis were conducted to present the effect pattern of
MMP13 in BC.
CONCLUSIONS: Our result can improve the understanding of researchers on the underlying mechanisms of BC bone metastasis.