Abstract
PurposeThis study aimed to determine the expression and clinical significance of proteins that are involved in lipid metabolism in human breast tumors.MethodsTumors from 476 breast cancer patients were used to construct tissue microarrays. Then, immunohistochemistry (IHC) for hormone-sensitive lipase (HSL), Perilipin 1 (PLIN1), fatty acid binding protein 4 (FABP4), carnitine palmitoyltransferase IA (CPT-1A), acyl-CoA oxidase 1 (ACOX-1), and fatty acid synthase (FASN) was performed on these microarrays.ResultsBreast tumors were classified into 4 subtypes: luminal A (n = 242; 50.8%), luminal B (n = 134; 28.2%), human epidermal growth factor receptor 2 (HER2) (n = 50; 10.5%), and triple negative breast cancer (TNBC) (n = 50; 10.5%). The expression of PLIN1 (p < 0.001), FABP4 (p = 0.029), CPT-1A (p = 0.001), ACOX-1 (p < 0.001), and FASN (p < 0.001) differed significantly among these tumor subtypes. Notably, PLIN1, CPT-1A, and FASN expression was highest in HER2 tumors and lowest in TNBC tumors. Similarly, the expression of FABP4 and ACOX-1 was highest in HER2 tumors and lowest in luminal A tumors. In addition, ACOX-1 positivity was associated with significantly shorter overall survival (p = 0.018). When tumor subtype was considered, FABP4 positivity was associated with significantly shorter disease-free survival (p = 0.005) and overall survival (p = 0.041) in TNBC.ConclusionLipid metabolism-related proteins are differentially expressed in different IHC subtypes of breast cancer and some are associated with decreased survival rates.
Highlights
In oncology, the Warburg effect describes a significant metabolic change in energy production from oxidative phosphorylation in normal cells to aerobic glycolysis in cancer cells [1]
Breast tumors were classified into 4 subtypes: luminal A (n = 242; 50.8%), luminal B (n = 134; 28.2%), human epidermal growth factor receptor 2 (HER2) (n = 50; 10.5%), and triple negative breast cancer (TNBC) (n = 50; 10.5%)
Perilipin 1 (PLIN1), CPT-1A, and fatty acid synthase (FASN) expression was highest in HER2 tumors and lowest in TNBC tumors
Summary
The Warburg effect describes a significant metabolic change in energy production from oxidative phosphorylation in normal cells to aerobic glycolysis in cancer cells [1] This definition is somewhat simplistic as tumors can use several different metabolic mechanisms to produce energy, depending on the type of tumor [2], which complicates targeted delivery of metabolic inhibitors to cancer cells. Carnitine palmitoyltransferase IA (CPT-1A) and acyl-CoA oxidase 1 (ACOX-1) are two important enzymes in this process [5,6,7] Aside from this process, lipid transport and uptake are an important and under-appreciated aspect of lipid metabolism in cancer [8,9]. It is becoming clear that lipid droplets are more than just passive storage components and are important in cancer as well, in particular for survival under stressful conditions [11,12], where lipid droplet proteins (HSL and PLIN1) play an important role
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