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Expression of Lipid Metabolism-Related Proteins in Metastatic Breast Cancer

 Yoon Yang Jung  ;  Hye Min Kim  ;  Ja Seung Koo 
 PLOS ONE, Vol.10(9) : e0137204, 2015 
Journal Title
Issue Date
Acyl-CoA Oxidase/biosynthesis ; Acyl-CoA Oxidase/genetics ; Adult ; Bone Neoplasms/metabolism ; Bone Neoplasms/secondary ; Brain Neoplasms/metabolism ; Brain Neoplasms/secondary ; Breast Neoplasms/genetics ; Breast Neoplasms/metabolism* ; Breast Neoplasms/pathology ; Carcinoma/genetics ; Carcinoma/metabolism ; Carcinoma/secondary* ; Carnitine O-Palmitoyltransferase/biosynthesis ; Carnitine O-Palmitoyltransferase/genetics ; Carrier Proteins/biosynthesis ; Carrier Proteins/genetics ; Estrogens ; Fatty Acid Synthase, Type I/biosynthesis ; Fatty Acid Synthase, Type I/genetics ; Fatty Acid-Binding Proteins/biosynthesis ; Fatty Acid-Binding Proteins/genetics ; Female ; Gene Expression Regulation, Neoplastic* ; Genes, erbB-2 ; Humans ; Kaplan-Meier Estimate ; Lipid Metabolism/genetics* ; Liver Neoplasms/metabolism ; Liver Neoplasms/secondary ; Lung Neoplasms/metabolism ; Lung Neoplasms/secondary ; Middle Aged ; Neoplasm Proteins/biosynthesis ; Neoplasm Proteins/genetics ; Neoplasms, Hormone-Dependent/genetics ; Neoplasms, Hormone-Dependent/metabolism ; Organ Specificity ; Perilipin-1 ; Phosphoproteins/biosynthesis ; Phosphoproteins/genetics ; Progesterone ; Proportional Hazards Models ; Receptor, ErbB-2/analysis ; Triple Negative Breast Neoplasms/genetics ; Triple Negative Breast Neoplasms/metabolism
PURPOSE: The tumor biology of metastatic breast cancers differ according to the metastatic sites, and the features of cancer metabolism may also be different. The aim of this study is to investigate the expression of lipid metabolism-related proteins in metastatic breast cancer according to metastatic site and discuss the clinical significance thereof. METHODS: Immunohistochemical staining for lipid metabolism-related proteins [fatty acid synthase (FASN), hormone-sensitive lipase (HSL), carnitine palmitoyltransferase IA (CPT-1A), acyl-CoA oxidase 1 (ACOX1), fatty acid binding protein 4 (FABP4,) and perilipin 1 (PLIN1)] was performed using a tissue microarray of 149 cases of metastatic breast cancer (bone metastasis = 39, brain metastasis = 37, liver metastasis = 21, and lung metastasis = 52). RESULTS: The expression levels of ACOX1 (p = 0.009) and FASN (p = 0.007) varied significantly according to metastatic site, with the highest expression in brain metastasis and the lowest expression in liver metastasis. ACOX1 positivity (p = 0.005) and FASN positivity (p = 0.003) correlated with HER-2 positivity. The expression of FASN was significantly higher in HER-2 type breast cancer, and lower in luminal A and TNBC type breast cancer (p<0.001). Among lipid metabolism-related proteins, PLIN1 positivity was found to be an independent poor prognostic factor on multivariate analysis (Hazard ratio: 4.979, 95% CI: 1.054-22.59, p = 0.043). CONCLUSION: Different expression levels of lipid metabolism-related proteins were observed according to metastatic site. The expression of ACOX1 and FASN was highest in brain metastasis. These results suggest that the metastatic site should be considered when using lipid metabolism inhibitors for targeted therapy.
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1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Koo, Ja Seung(구자승) ORCID logo https://orcid.org/0000-0003-4546-4709
Kim, Hye Min(김혜민) ORCID logo https://orcid.org/0000-0002-2899-9480
Jung, Yoon Yang(정윤양)
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