Monounsaturated fatty acids in serum triacylglycerols are associated with response to neoadjuvant chemotherapy in breast cancer patients

Abstract

Changes in cellular lipid metabolism are a common feature in most solid tumors, which occur already in early stages of the tumor progression. However, it remains unclear if the tumor-specific lipid changes can be detected at the level of systemic lipid metabolism. The objective of this study was to perform comprehensive analysis of lipids in breast cancer patient serum samples. Lipidomic profiling using an established analytical platform was performed in two cohorts of breast cancer patients receiving neoadjuvant chemotherapy. The analyses were performed for 142 patients before and after neoadjuvant chemotherapy, and the results before chemotherapy were validated in an independent cohort of 194 patients. The analyses revealed that in general the tumor characteristics are not reflected in the serum samples. However, there was an association of specific triacylglycerols (TGs) in patients' response to chemotherapy. These TGs containing mainly oleic acid (C18:1) were found in lower levels in those patients showing pathologic complete response before receiving chemotherapy. Some of these TGs were also associated with estrogen receptor status and overall or disease-free survival of the patients. The results suggest that the altered serum levels of oleic acid in breast cancer patients are associated with their response to chemotherapy.Breast cancer is the most common cancer in women worldwide. In the western world, approximately one in eight women will develop an invasive breast carcinoma. The major treatment options for breast cancer are surgery, radiotherapy, chemotherapy as well as hormonal and antibody therapies. Neoadjuvant chemotherapy provides an equally effective alternative to adjuvant chemotherapy.

Lipid desaturation – the next step in targeting lipogenesis in cancer?

“…Interestingly, soraphen A treated tumour cells showed a higher degree of lipid peroxidation when exposed to oxidative stress and increased sensitivity towards chemotherapeutic agents . Furthermore, increased levels of oleic acid in the serum of breast cancer patients were predictive of poor response to adjuvant chemotherapy . While it is unlikely that serum FA levels are determined by desaturase activity within the tumour, this finding may provide interesting diagnostic information .…”

“…Furthermore, increased levels of oleic acid in the serum of breast cancer patients were predictive of poor response to adjuvant chemotherapy . While it is unlikely that serum FA levels are determined by desaturase activity within the tumour, this finding may provide interesting diagnostic information .…”

Advances in Lipidomics for Cancer Biomarkers Discovery

“…De novo lipogenesis increased most solid tumors early on, potentially affecting the chemo-sensitivity of cancer cells. In an effort to investigate the potential predictive value of changes in lipidome, Hilvo et al explored if the lipidomic profiles are associated with pathologic complete response (pCR) in breast cancer patients, receiving neoadjuvant chemotherapy [61]. This study highlighted that serum triacylglycerol (TGs) containing C18:1 fatty acyl chains were at lower concentrations in patients with pCR.…”

“…For example, phosphatidyloserines (PSs) were found differentially expressed in urines of both breast [53] and prostate [64] cancer patients. Serum triacylglycerols (TGs) and linolenic acid seem to have predictive value of therapy response in cases of breast cancer patients receiving neoadjuvant chemotherapy [61,62], whereas plasma levels of different LPCs in colorectal cancer [72] or in prostate cancer [69] were also described. These studies provide a cancer lipid fingerprint in different accessible biofluids, thereby opening the way for the discovery of diagnostic biomarkers able to properly classify cancer patients.…”

Variations and heredity in bacterial colonies

“…These data was also used to perform clustering by PLS-DA method (“plsda” function in R, mixOmics package 27 ), that is widely used as discrimination method in chemometrics 28 or to reduce dimensions in highly correlated data e.g reflectance data 29 . Additionally, 2 other clones were considered: rdf variant, what is taken as pigmented over the whole area and M variant as entirely non-pigmented.…”