Expression analyses of fatty acid binding proteins (FABPs) in breast cancer subtypes: implications for immune modulation and clinical outcomes.

[BACKGROUND] Fatty acid binding proteins (FABPs) are key regulators of lipid metabolism and are expressed in the stroma of breast cancer. However, their roles in different breast cancer subtypes remain unclear. This study explored the expression patterns of FABPs across breast cancer subtypes and examined their associations with immune cell infiltration and clinical features using large datasets, with validation performed through testing in breast cancer cell lines and human tissue samples.

[METHODS] A comprehensive bioinformatic analysis was performed using The Cancer Genome Atlas (TCGA) and Genomic Spatial Event database (GSE) datasets to investigate FABPs' expression patterns and prognostic significance in breast cancer. Prognostic outcomes were evaluated with Kaplan-Meier analysis via PROGgeneV2, and clinicopathological associations, including estrogen receptor (ER)/progesterone receptor (PR) status and tumor grades, were examined using Breast Cancer Gene-Expression Miner v5.1. Immune cell infiltration correlations were assessed through TIMER2.0. Experimental validation was performed by quantitative real-time polymerase chain reaction (qRT-PCR) in breast cancer cell lines (MCF7 and MDA-MB-231) and the non-malignant breast epithelial cell line MCF10A. Independent validation was further conducted in a cohort of frozen breast cancer tissues (n=38).

[RESULTS] FABPs exhibited distinct expression patterns across breast cancer subtypes. FABP4 was associated with the luminal A subtype and ER-positive status, FABP5 and FABP7 with the basal subtype and ER-negative status, and FABP6 with the human epidermal growth factor receptor 2 (HER2)-enriched subtype. Functional analyses suggested their involvement in immune modulation and other biological processes. FABP expression correlated significantly with immune cell infiltration, particularly CD8 T cells. Although subtype-related trends were observed in breast cancer tissue validation, no statistically significant differences in FABP4-FABP7 mRNA expression were detected among molecular subtypes, likely reflecting limited sample size. In vitro validation showed that FABP4 and FABP5 were downregulated in MCF7 and MDA-MB-231 compared to the non-malignant MCF10A. MDA-MB-231 exhibited FABP5 expressions higher than MCF7, whereas FABP4, FABP6, and FABP7 were upregulated in MCF7 compared to MDA-MB-231. These findings are aligned with tissue data from TCGA and underscore the subtype-specific expression patterns of FABPs.

[CONCLUSIONS] This study identified distinct expression patterns of FABPs across breast cancer subtypes and highlighted their potential roles in immune modulation. These findings offer new insights into the diverse functions of FABPs in breast cancer and their implications for prognosis.