Abstract
“Surrogate” definitions of intrinsic subtypes, which imply the Ki67 proliferation marker, help to clinically distinguish luminal breast carcinomas (Lum BC). Here, mass spectrometry–based proteomics can help analyse the protein content of malignant and normal cells and eventually distinguish patient samples from healthy controls at the molecular level. In this work, peripheral blood CD14 + monocyte proteomes of the LumA, LumB-HER2 − and LumB-HER2 + subtypes and those with benign disease were compared to healthy controls (HCs). Among differentially expressed proteins (DEPs), SRSF1, CSTB, KRT2, KRT5, HEL-S-11, APOB, APOE and ITGA2B are considered as significantly changed in all Lum BC vs HCs comparisons (FC ≥ 1.4 or ≤ 0.7, adjusted P-value ≤ 0.05), while the benign vs HCs comparison showed that KRT2 and KRT5 were common DEPs for all disease groups. APOB, APOE, CSTB, HEL-S-11, SRSF1, and ITGA2B had AUC ≥ 0.6 in all Lum BC cohorts and may serve as feasible classifiers of random individuals. ENO1, KRT1, and AIDB were among the top 10 hits in LumA, LumB-HER2 − and LumB-HER2+, respectively, and can also likely be related to Lum BC. GSEA (P-value < 0.05, FDR ≤ 0.25) identified significantly enriched KEGG Gonadotropin release hormone, KEGG Leukocyte trans-endothelial migration, and KEGG Calcium signalling pathways that were all downregulated in LumA. In LumB-HER2-, KEGG Ribosome and KEGG Lysosome pathways were upregulated and downregulated, respectively, while in LumB-HER2+, the HALLMARK MYC-Targets V2 pathway was found downregulated. The suggested study represents a preliminary research and overview of feasible candidate biomarker proteins in peripheral blood CD14 + monocytes of different Lum BC subtypes. Such proteins may reflect BC-related immune responses and therefore could help to subcategorise disease cohorts using a comparative proteomic approach. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-026-39686-y.