Integration of Metabolomics and Expression of Glycerol-3-phosphate Acyltransferase (GPAM) in Breast Cancer—Link to Patient Survival, Hormone Receptor Status, and Metabolic Profiling

Abstract

Changes in lipid metabolism are an important but not well-characterized hallmark of cancer. On the basis of our recent findings of lipidomic changes in breast cancer, we investigated glycerol-3-phosphate acyltransferase (GPAM), a key enzyme in the lipid biosynthesis of triacylglycerols and phospholipids. GPAM protein expression was evaluated and linked to metabolomic and lipidomic profiles in a cohort of human breast carcinomas. In addition, GPAM mRNA expression was analyzed using the GeneSapiens in silico transcriptiomics database. High cytoplasmic GPAM expression was associated with hormone receptor negative status (p = 0.013). On the protein (p = 0.048) and mRNA (p = 0.001) levels, increased GPAM expression was associated with a better overall survival. Metabolomic analysis by GC-MS showed that sn-glycerol-3-phosphate, the substrate of GPAM, was elevated in breast cancer compared to normal breast tissue. LC-MS based lipidomic analysis identified significantly higher levels of phospholipids, especially phosphatidylcholines in GPAM protein positive tumors. In conclusion, our results suggest that GPAM is expressed in human breast cancer with associated changes in the cellular metabolism, in particular an increased synthesis of phospholipids, the major structural component of cellular membranes.

Glycerol-3-phosphate Acyltransferase 1 Promotes Tumor Cell Migration and Poor Survival in Ovarian Carcinoma

“…In breast cancer, higher GPAM expression was associated with longer MFS or DFS in two cohorts for at least one probe set (GSE9195: HR ¼ 0.36, P ¼ 0.044; GSE42568: HR ¼ 0.67-0.73, P ¼ 0.016-0.019), supporting previous findings (23). Conversely, when the analysis was performed stratified according to ER and HER2 status, GPAM was found to be associated with shorter MFS or DFS in HER2-positive patient subsets in two cohorts (GSE19615: HR ¼ 2.62, P ¼ 0.040; GSE21653: HR ¼ 1.46, P ¼ 0.040; Supplementary Table S9).…”

Myc Expression Drives Aberrant Lipid Metabolism in Lung Cancer

“…Although the precise role of aberrant lipid biosynthesis is unknown, several studies have shown that the lipid profile has been linked to survival, ER status, and tumor grade in human breast cancer (7,8). The lipid composition of tumors is also affected by dynamic processes, having been observed to vary with cell proliferation, apoptosis, and necrosis (9).…”

Disruption of tumor suppressor gene Hint1 leads to remodeling of the lipid metabolic phenotype of mouse liver

“…Conditions of the mass spectrometer were as above but with a run time of 18 min. For liver lipidomics, the protocol was adapted in part from a published method ( 29 ). Accurately weighed liver samples ( ‫ف‬ 50 mg) were homogenized in water-methanol (43:57 v/v) in a Precellys ® 24 bead homogenizer (Bertin Corp., Rockville, MD).…”