Exploration of the Relationship between Macrophage-Related Proteins and the Risk and Prognosis of Breast Cancer

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.

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.

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).

Elevated levels of macrophage inflammatory protein 1A may increase the risk of breast cancer and lead to poorer patient outcomes.