Breast Cancer Bone Metastasis: Novel Prognostic Biomarkers Identified.

The impact of lipid metabolism on the development and prognosis of bone metastasis from breast cancer (BRCA) is currently unknown. Sequencing data of BRCA samples in this study were obtained from the University of California, Santa Cruz (UCSC) Xena database. The differentially expressed genes (DEGs1) between the BRCA group and the control group, the differentially expressed genes (DEGs2) between the bone metastasis group and the non-bone metastasis group, and the lipid metabolism score-related genes (LMSRGs) were intersected to obtain LMSRGs (DE-LMSRGs). Biomarkers were obtained using univariate logistic regression analysis, support vector machine recursive feature elimination (SVM-RFE) and multivariate logistic regression analysis for Correlation Analysis, Gene Set Enrichment Analysis, Immunohistochemistry, Co-creation of Networks, and Drug Prediction, and then analyses were performed using Immunohistochemistry, Western blot analyses to validate the samples. We identified two biomarkers (Regulator of G-protein Signaling 9 Binding Protein (RGS9BP) and suppressor of cytokine signaling 3 (SOCS3)). There were nine immune cells that were markedly differential between bone metastasis and non-bone metastasis groups, such as activated dendritic cell, neutrophil, plasmacytoid dendritic cell, etc. Then, the lncRNA-miRNA-mRNA network was created, including the regulated relationship pairs HLX-AS1-hsa-mir-541-SOCS3, ZNF337-AS1-hsa-mir-541-SOCS3. Molecular docking analyses have demonstrated that the complexes formed by SOCS3 alongside folic acid, estradiol, and S-Adenosylmethionine exhibit heightened stability. Similarly, the pairing of RGS9BP with benzopyrene showcases a notable degree of stability. Finally, the biomarkers were associated with angiogenesis scores and most angiogenesis related genes (ARGs). Our study identified two potential biomarkers (RGS9BP and SOCS3) for prognostic evaluation of bone metastasis patients with BRCA. These findings provided a scientific reference for further research on bone metastasis in BRCA patients.

Supplementary information: The online version contains supplementary material available at 10.1007/s43657-025-00221-0.