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Background: Macrophage-related proteins play a crucial role in breast cancer. The present study explored the relationship between macrophage-related proteins and breast cancer using Mendelian randomization (MR) for genetic variations and bioinformatics methods for transcriptomics.
Methods: Genetic instruments associated with macrophage migration inhibitory factor (MIF), macrophage inflammatory protein 1α (MIP-1α), macrophage inflammatory protein 1β (MIP-1β), and granulocyte macrophage colony-stimulating factor (GM-CSF) were gathered from genome-wide association studies (GWAS). The MR analysis was conducted using R software packages ‘TwoSampleMR’ and ‘MRPRESSO’, employing MR-Egger, in-verse-variance weighted (IVW), weighted median, simple mode, and MR-PRESSO algorithms. In addition, data from the UCSC Xena database provided the TCGA BRCA dataset for a 5-year overall survival analysis of MIP-1α.
Results: IVW analysis showed a significant positive association between MIP-1α and breast cancer incidence (OR = 1.0837, 95% CI: 1.0284 - 1.142), and the MR-PRESSO result also confirmed a causal relationship between them (OR = 1.0789, 95% CI: 1.0266 - 1.1338). There was no significant causal relationship found between MIF, MIP-1B, GM-CSF, and breast cancer. Survival analysis revealed that CCL3 was associated with prognosis in breast cancer patients in the Cox proportional-hazard model (HR = 1.5000, 95% CI: 1.0110 - 2.2250).
Conclusions: Elevated levels of macrophage inflammatory protein 1A may increase the risk of breast cancer and lead to poorer patient outcomes.
DOI: 10.7754/Clin.Lab.2025.241128
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