Exploration of prognosis and immunometabolism landscapes in ER+ breast cancer based on a novel lipid metabolism-related signature

Abstract

IntroductionLipid metabolic reprogramming is gaining attention as a hallmark of cancers. Recent mounting evidence indicates that the malignant behavior of breast cancer (BC) is closely related to lipid metabolism. Here, we focus on the estrogen receptor-positive (ER+) subtype, the most common subgroup of BC, to explore immunometabolism landscapes and prognostic significance according to lipid metabolism-related genes (LMRGs).MethodsSamples from The Cancer Genome Atlas (TCGA) database were used as training cohort, and samples from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), Gene Expression Omnibus (GEO) datasets and our cohort were applied for external validation. The survival-related LMRG molecular pattern and signature were constructed by unsupervised consensus clustering and least absolute shrinkage and selection operator (LASSO) analysis. A lipid metabolism-related clinicopathologic nomogram was established. Gene enrichment and pathway analysis were performed to explore the underlying mechanism. Immune landscapes, immunotherapy and chemotherapy response were further explored. Moreover, the relationship between gene expression and clinicopathological features was assessed by immunohistochemistry.ResultsTwo LMRG molecular patterns were identified and associated with distinct prognoses and immune cell infiltration. Next, a prognostic signature based on nine survival-related LMRGs was established and validated. The signature was confirmed to be an independent prognostic factor and an optimal nomogram incorporating age and T stage (AUC of 5-year overall survival: 0.778). Pathway enrichment analysis revealed differences in immune activities, lipid biosynthesis and drug metabolism by comparing groups with low- and high-risk scores. Further exploration verified different immune microenvironment profiles, immune checkpoint expression, and sensitivity to immunotherapy and chemotherapy between the two groups. Finally, arachidonate 15-lipoxygenase (ALOX15) was selected as the most prominent differentially expressed gene between the two groups. Its expression was positively related to larger tumor size, more advanced tumor stage and vascular invasion in our cohort (n = 149).DiscussionThis is the first lipid metabolism-based signature with value for prognosis prediction and immunotherapy or chemotherapy guidance for ER+ BC.

Identification of hub genes significantly linked to tuberous sclerosis related-epilepsy and lipid metabolism via bioinformatics analysis

“…Specifically, we downloaded the datasets GSE16969 ( 13 ) and GSE62019 ( 14 ), as well as single cell sequencing data from GSE201048 ( 15 ) ( Supplementary Table 1 ). Lipid metabolism related pathways (LMRPs) were also sourced from the following PubMed articles: PMID35222371 ( 16 ), PMID36091041 ( 17 ), PMID36860853 ( 18 ), and PMID37469520 ( 19 ) ( Supplementary Table 2 ). The design and workflow of this study are shown in Figure 1 .…”

Analyzing the impact of metabolism on immune cells in tumor microenvironment to promote the development of immunotherapy

“…In addition, immune cells can also make use of the ketone bodies produced by the fatty acids oxidation to obtain energy (20). Lipids include phospholipids, cholesterol, triglycerides, fatty acids, and many other types (39)(40)(41)(42). Lipid metabolism includes anabolism and catabolism, and the catabolism is commonly known as b-oxidation (43).…”