The clinical signature of genetic variants and serum levels of macrophage migration inhibitory factor in Egyptian breast cancer patients

• Published in: Breast cancer research and treatment Vol. 208; no. 1; pp. 57 - 66
• Main Authors: Seliem, Mahmoud A., Mohamadin, Ahmed M., El-Sayed, Mohamed I. Kotb, Ismail, Yahia, El-Husseiny, Ahmed A.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.11.2024; Springer Nature B.V
• Subjects: Adaptive immunity; Adult; Aged; Alleles; Biomarkers, Tumor - blood; Biomarkers, Tumor - genetics; Breast cancer; Breast Neoplasms - blood; Breast Neoplasms - genetics; Case-Control Studies; Egypt - epidemiology; Enzyme-linked immunosorbent assay; Female; Females; Genetic diversity; Genetic Predisposition to Disease; Genotype; Genotyping; Humans; Innate immunity; Intramolecular Oxidoreductases - blood; Intramolecular Oxidoreductases - genetics; Leukocyte migration; Macrophage migration inhibitory factor; Macrophage Migration-Inhibitory Factors - blood; Macrophage Migration-Inhibitory Factors - genetics; Medicine; Medicine & Public Health; Middle Aged; Oncology; Pathogenesis; Patients; Polymorphism, Single Nucleotide; Progesterone; ROC Curve; Serum levels; Tumor markers; Variants; Egypt; Tumor marker; Serum MIF; Breast cancer; Immunity; Polymorphism
• ISSN: 0167-6806; 1573-7217; 1573-7217
• DOI: 10.1007/s10549-024-07393-9

Purpose Macrophage migration inhibitory factor (MIF) is an integral cytokine for the modulation of both innate and adaptive immunity and is involved in the pathogenesis of various cancers. However, conflicting findings on the relationship between MIF polymorphisms and breast cancer (BC) have been reported in earlier research. We investigated the clinical value of serum MIF levels and the association between MIF rs1049829 and rs755622 variants with their serum levels and propensity to develop BC. Methods A total of 133 treatment-naïve Egyptian BC females and 126 apparently healthy controls were matriculated in this case–control study. The serum MIF protein levels were quantified by ELISA, whereas the genotyping was executed utilizing the TaqMan® allelic discrimination assay. Results A significant increase in the serum MIF level in BC cases was observed in comparison to control subjects ( P  < 0.0001), with a diagnostic potential to discriminate BC with 92.5% sensitivity and 73.7% specificity at a cut-off value > 9.47 ng/mL. Besides, a significant difference in serum MIF level was observed in BC cases with progesterone receptor (PR) negativity compared to those with PR positivity ( P  = 0.046). Moreover, a significant association was depicted between the rs1049829 variant of MIF gene and the protective effect against BC meanwhile the rs755622 variant demonstrated no significant link with BC risk. Conclusions This study revealed that serum MIF levels may be regarded as a promising serum tumor marker for BC. Also, the rs1049829 variant of the MIF gene is considered a protective candidate against BC. Graphical Abstract