Identification of Lipid Droplet-Associated Genes in Breast Cancer Patients

Author:

Dogan Senol12ORCID,Leopold Jenny3ORCID,Hoffmann Daniel T.1,Kubitschke Hans1,Blauth Eliane1,Ficorella Carlotta1,Zschau Amelie4,Schiller Jürgen3ORCID,Käs Josef A.1ORCID

Affiliation:

1. Peter Debye Institute, Faculty of Physics and Earth Science, Leipzig University, Linnéstr. 5, 04103 Leipzig, Germany

2. Department of Gynecology, Medical Center, University of Leipzig, 04103 Leipzig, Germany

3. Institute for Medical Physics and Biophysics, Faculty of Medicine, Leipzig University, Härtelstr. 16-18, 04107 Leipzig, Germany

4. Werner-Heisenberg-Gymnasium Leipzig, Renftstraße 3, 04159 Leipzig, Germany

Abstract

Lipid droplets (LDs) are known to be involved in the invasion and migration of breast cancer (BC) cells. This study aimed to identify LD-associated genes as prognostic markers in BC through comprehensive literature research and integration with lipid composition studies in BC cell lines. The GEPIA platform was used to analyze the differential expression of LD-associated genes in BC. The lipid composition of cell lines (MCF-10A, MDA-MB 436 and 231) was obtained by extraction and thin-layer chromatography coupled with mass spectrometry (MS). Additionally, cell lines were co-cultured with fatty tissue and analyzed by confocal fluorescence microscopy. A total of 143 genes were identified as LD-associated genes through literature research and were subsequently analyzed using GEPIA. Among these, three genes were found to be over-expressed and 45 under-expressed in BC. Notably, FABP7 showed a statistically significant rank for all bioinformatics criteria as a prognostic factor. Experimental results showed only minor changes from MCF-10A to both MDA-MB cell lines for apolar lipids (triacylglycerols and cholesteryl esters) compared to phospholipids (PLs). Microscopic analyses showed that MDA-MB-231 had larger LDs compared to MCF-10A after 10 days of cultivation. Our bioinformatics analysis identified 26 genes that play important roles in metastatic transition in BC via LD-related mechanisms, though these findings could be only partially confirmed by experimental lipid compositional analyses, so far.

Funder

German Research Council

Publisher

MDPI AG

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