Expression profiling of T cell and B cell activation genes and immunoglobulin G subclasses in Egyptian breast cancer patients

Abstract

The expression patterns of T and B cell activation genes, along with Immunoglobulin G (IgG) subclasses, offer key insights into breast cancer progression. This study examined expression changes in four breast cancer subtypes - Luminal B HER2+, Luminal B HER2−, Luminal-like, and Triple Negative Breast Cancer (TNBC) - compared to healthy controls. Serum IgG subclass concentrations were also evaluated across these subtypes. Using the RT² Profiler QPCR array, expression of 84 genes was assessed, revealing 39 upregulated and 7 downregulated genes in Luminal B HER2+, 33 and 11 in Luminal B HER2−, 47 and 15 in Luminal-like, and 36 and 12 in TNBC, respectively. Four genes involved in antibody production were commonly altered across all subtypes. CD27 (P = 0.0122) showed fold changes of 5.60, 87.39, 49.93, and 109.38, while CD28 (P = 0.0014) increased by 54.13, 15.54, 26.95, and 54.41-fold. CD40 (P = 0.0003) was upregulated with 31.88, 15.28, 23.82, and 19.25 folds across subtypes, as was IL7 (P = 0.0002), with 2.89, 2.84, 3.52 and 3.28-fold increase. Conversely, LAG3 (P = 0.0347) was consistently downregulated (fold changes: 0.01, 0.01, 0.04 and 0.45). Immune checkpoint analysis revealed significant upregulation of CD274 (P = 0.0045), CD47 (P = 0.0432), CD276 (P = 0.0310) and TLR9 (P = 0.0081), while LAG3 (P = 0.0347) were significantly downregulated. ELISA-based serum analysis showed significantly elevated IgG1 across all subtypes (P < 0.007). IgG2 increased in Luminal B HER2− (P = 0.0007) and decreased in TNBC (P = 0.0004). IgG3 was reduced in Luminal B HER2+, Luminal-like, and TNBC (P < 0.035), while IgG4 increased in Luminal B HER2+ and HER2− but decreased in TNBC. These findings highlight pronounced, subtype-specific adaptive and innate immune responses in breast cancer, reflecting the intricate landscape of immune modulation in tumorigenesis.