A Novel Risk Model Based on Lipid Metabolism-Associated Genes Predicts Prognosis and Indicates Immune Microenvironment in Breast Cancer.

ABSTRACT

BACKGROUND: Breast cancer (BRCA) is the most common tumor in women, and lipid metabolism involvement has been demonstrated in its tumorigenesis and development. However, the role of lipid metabolism-associated genes (LMAGs) in the immune microenvironment and prognosis of BRCA remains unclear. METHODS: A total of 1076 patients with BRCA were extracted from The Cancer Genome Atlas database and randomly assigned to the training cohort (n = 760) or validation cohort (n = 316). Kaplan-Meier analysis was used to assess differences in survival. Consensus clustering was performed to categorize the patients with BRCA into subtypes. Using multivariate Cox regression analysis, an LMAG-based prognostic risk model was constructed from the training cohort and validated using the validation cohort. The immune microenvironment was evaluated using the ESTIMATE and tumor immune estimation resource algorithms, CIBERSORT, and single sample gene set enrichment analyses. RESULTS: Consensus clustering classified the patients with BRCA into two subgroups with significantly different overall survival rates and immune microenvironments. Better prognosis was associated with high immune infiltration. The prognostic risk model, based on four LMAGs (MED10, PLA2G2D, CYP4F11, and GPS2), successfully stratified the patients into high- and low-risk groups in both the training and validation sets. High risk scores predicted poor prognosis and indicated low immune status. Subgroup analysis suggested that the risk model was an independent predictor of prognosis in BRCA. CONCLUSION: This study demonstrated, for the first time, that LMAG expression plays a crucial role in BRCA. The LMAG-based risk model successfully predicted the prognosis and indicated the immune microenvironment of patients with BRCA. Our study may provide inspiration for further research on BRCA pathomechanisms.