Key result
In patients with metastatic breast cancer, PLIN1 positivity was an independent poor prognostic factor for overall survival (HR 4.979), while ACOX1 and FASN expression varied significantly by metastatic site.
Observational (n=149)
No
Hazard Ratio: 4.979 (95% CI 1.054–22.59)
p-value: p=0.043
Lipid metabolism-related proteins show differential expression based on metastatic site in breast cancer, with PLIN1 serving as a poor prognostic factor.
PLIN1 positivity may identify higher-risk metastatic breast cancer; hypothesis-generating for lipid metabolism markers and requires prospective validation before any clinical use.
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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Jung et al. (2015) conducted an observational in Metastatic breast cancer (n=149). PLIN1 positivity vs. PLIN1 negativity was evaluated on Overall survival (HR 4.979, 95% CI 1.054-22.59, p=0.043). In patients with metastatic breast cancer, PLIN1 positivity was an independent poor prognostic factor for overall survival (HR 4.979), while ACOX1 and FASN expression varied significantly by metastatic site.
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