Peripheral Blood Mononuclear Cell Expression Profile of Proliferation-, Ferroptosis-, and Immune-Related Targets in...

Background and Objectives: This study evaluated eight targets related to proliferation (miR-21, miR-210, PTEN, and mTOR), ferroptosis regulation (SLC7A11, GPX4, and miR-214), and immune regulation (STAT3) in bulk (unfractionated) peripheral blood mononuclear cells (PBMCs) from patients with breast cancer. Their exploratory discriminative performance and associations with clinicopathological characteristics, including immunohistochemical parameters, were also examined. Materials and Methods: Target expression was quantified by qRT-PCR in PBMCs from 41 patients with histopathologically confirmed breast cancer and 30 healthy controls. Immunohistochemistry-defined surrogate subtypes (hereafter, IHC-defined subtypes) were assigned according to ER, PR, HER2 and Ki-67 status. Between-group comparisons were performed using the independent-samples t-test or the Mann-Whitney U test; multiple comparisons were corrected using the Benjamini-Hochberg false discovery rate (BH-FDR) method. Exploratory discriminative performance was determined by ROC analysis with 2000-iteration bootstrap confidence intervals. Directional consistency was examined in two independent PBMC GEO datasets (GSE27562, GSE47862); this was a directional comparison rather than formal external validation. Results: Seven of the eight targets differed significantly after BH-FDR correction: STAT3, mTOR, SLC7A11, miR-21, and miR-210 were upregulated, whereas PTEN and miR-214 were downregulated. In this exploratory, single-cohort case-control study, the largest exploratory single-marker AUCs were observed for STAT3, PTEN, miR-210 and SLC7A11. No association with clinicopathological parameters survived multiple-testing correction. In a post hoc exploratory comparison, PBMC PTEN levels were lower in TNBC (n = 13) than in non-TNBC cases (n = 28), but this difference did not remain significant after BH-FDR correction (Mann-Whitney U, p = 0.024; BH-FDR p = 0.193). Conclusions: Breast cancer was associated with distinct expression patterns in bulk PBMCs, including increased miR-21 and mTOR expression with decreased PTEN expression, increased SLC7A11 with decreased miR-214 expression, and increased STAT3 expression. Five significant pairwise correlations were identified among the measured targets. Because these findings were derived from transcript-level measurements in unfractionated PBMCs, they do not establish functional pathway activation or ferroptosis resistance. Lower PBMC PTEN expression in TNBC reached nominal but not FDR-corrected significance, so no clinicopathological association is claimed.