Poster Presentation HUPO 2019 - 18th Human Proteome Organization World Congress

Global lipidomics reveals broad dysregulation of lipid metabolism in triple negative breast cancer development (#651)

Yan Li 1 , Fangmeng Fu 1 , Ling Lin 2 , Songping Lin 1 , Jinxing Lv 1 , Chuan Wang 1
  1. Department of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
  2. Institutes of Biomedical Sciences of Shanghai Medical School, Fudan University, Shanghai, China

Triple Negative Breast Cancer (TNBC) is an aggressive disease, accounting for 15% -23.8% of all breast cancers. Due to the complexity and diversity of lipid molecules, along with the challenges in analytical techniques development and comprehensive lipid database construction, altered lipid composition and reprogrammed lipid metabolism have not been fully elucidated during TNBC progression. Here, we performed a highly sensitive shotgun lipidomic approach to explore the global lipidome in tumor tissues and corresponding para-tumor tissues from Grade I-II and Grade III TNBC patients. Totally, 1556 intact lipids were identified in different stage of TNBC tissues and paired para-cancerous tissues. Palmitic acyl (C16:0)-containing glycerophospholipids (GPs) were significantly reduced in tumor tissues compared with adjacent nontumor tissues, while C18:0 and C20:5-containing GPs were remarkably upregulated. Systematic lipidomic changes occurring in different groups were then assessed by two widely used multivariate methods - principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA). The first principal component (PC1) accounted for 69% of the total variance and separated TNBC tumor tissues from corresponding para-tumor tissues. The second principal component (PC2) accounts for 12.1% of the variance in the data. PLS-DA was applied to enhance the separation between the groups. PE(18:0/18:2) with the highest VIP value was the most powerful group discriminator in differentiating tumor tissues from para-tumor tissues. It is interesting to note that the decreased saturated fatty acyl containing GPs (such as C16:0 and C14:0) and the increased unsaturated fatty acyl comprising GPs (such as C18:0, C20:4 and C20:5) in tumor tissues compared with para-tumor ones. Thus we further examined the effects of palmitic acid treatment on cell proliferation and invasion ability in vitro via MDA-MB-231 cell line. Our data collectively herald the biomedical potential of using altered lipid metabolism for treating triple negative breast cancer.