Development and validation of an immune-related diagnostic signature for breast cancer bone metastasis.

Bone is one of the distant metastases in patients with Breast Cancer (BC). However, the mechanism of BC bone metastasis is not fully understood. The aim of this study was to investigate the potential mechanisms linking bone metastasis-related genes and BC.The training set consisted of data from The Cancer Genome Atlas (TCGA)-BC dataset, which included 1,104 breast cancer samples (comprising 50 with bone metastasis and 1,052 without) and 114 adjacent normal samples. Differentially expressed genes (DEGs1) between breast cancer and normal tissues, as well as DEGs2 between breast cancer bone metastatic and non-bone metastatic tissues, were identified. Weighted gene co-expression network analysis (WGCNA) was then applied to screen breast cancer-related module genes. The intersection of these three sets was taken to obtain candidate genes. Diagnostic genes were identified via univariate Cox regression and Least Absolute Shrinkage and Selection Operator (LASSO) analysis to construct a risk model, which was subsequently validated using the Gene Expression Omnibus (GEO) dataset GSE20685 (327 samples, validation set). Furthermore, immune infiltration analysis, mRNA-miRNA-lncRNA regulatory network construction, and drug sensitivity analysis were performed in the training set. Finally, quantitative reverse transcription polymerase chain reaction (qRT-PCR) was conducted on clinical samples for validation.There were 756 DEGs between BC and control samples. A sum of 6 BC-related modules were acquired by WGCNA. After screening, 997 bone metastasis-associated genes and 73 candidate genes were acquired. A total of 6 diagnostic genes, namely ABHD8, ESRRA, DHPS, ISOC2, MRPL34 and OGFR, were obtained to construct the risk model. Results of the immune microenvironment analysis revealed that the high-risk group exhibited lower levels of certain immune cells, such as T cells and CD8+ T cells. Based on the public database,ESRRA was regulated by various miRNAs, such as hsa-miR-185-3p, hsa-miR-2115-5p. Based on the results of molecular docking experiments, a sum of 67 drugs had significant differences in IC50 between two risk subgroups. Transcriptomic data from TCGA indicated that all six diagnostic genes were significantly upregulated in the BC group (p < 0.05). However, qRT-PCR validation showed that ESRRA and OGFR were significantly downregulated in the BC group (p < 0.05), while the expression trends of the remaining four genes were consistent with the transcriptomic data.We explored the diagnostic genes (ABHD8, ESRRA, DHPS, ISOC2, MRPL34, and OGFR) of bone metastasis in BC, providing a reference for disease-related study.