Comprehensive lipid profiling of plasma in patients with benign breast tumor and breast cancer reveals novel biomarkers

Abstract

Abnormal lipid metabolism is a common feature in most solid tumors, and occurs in early stages of the tumor progression. As benign breast tumor is different from malignant tumor of breast cancer, it is particularly important to take benign breast tumor into consideration when investigating cancer biomarkers. In this study, by using a normal-phase/reversed-phase two-dimensional liquid chromatography-mass spectrometry (NP/RP 2D LC-MS) method, we conducted comprehensive lipid profiling in human plasma obtained from six benign breast tumor patients and five breast cancer patients, as well as nine healthy controls. As a result, 512 lipid species were successfully identified. Principal component analysis allowed clear separation of the three groups. Quantitative analysis revealed that many lipid contents were similar in benign and malignant breast tumors compared with controls, and these were proposed as potential breast tumor biomarkers other than breast cancer biomarkers. Two phosphatidylinositol (PI) species, including PI (16:0/16:1) and PI (18:0/20:4), could differentiate between benign and malignant breast tumors, as well as breast cancer patients and healthy controls, indicating that they could be utilized as potential breast cancer biomarkers. In addition, PI (16:0/18:1), phosphatidylglycerol (36:3), and glucosylceramide (d18:1/15:1) were demonstrated to be potential biomarkers to evaluate the level of malignancy of breast tumor. Taken together, our results indicate the usefulness of lipid profiling in the discrimination between patients with breast cancer and non-carcinoma lesions, which might provide assistance in clinical diagnosis.

Recent advances in lipidomics for disease research

“…However, as a cancer biomarker should differentiate breast cancer from healthy control, as well as benign breast tumor, the proposed biomarkers for breast cancer in these studies need further confirmation. By introducing benign breast tumor group, our group provided a more detailed classification of lipid biomarker . Twentry six lipid species were identified as potential biomarkers for breast tumor, while two phosphatidylinositol (PI) species, including PI (16:0_16:1) and PI (18:0_20:4) could be utilized as potential breast cancer biomarkers.…”

Plasma lipidomics profiling identified lipid biomarkers in distinguishing early-stage breast cancer from benign lesions

“…However, most of these studies have just focused on total levels of lipids in cancer patients, and only a few of them included patients with benign breast diseases. Recently, Yang et al performed a comprehensive evaluation of plasma lipid profiles with benign breast disease patients in only 5 breast cancer cases and 6 benign patients, indicating the diagnostic efficiency of the lipid markers in these diseases [19]. …”

Liquid extraction surface analysis nanospray electrospray ionization based lipidomics for in situ analysis of tumor cells with multidrug resistance

“…So, increased levels of PIP3, a crucial signaling lipid involved in the PI3K/AKT pathway, could suppress apoptosis thus favoring cancer progression, partly through mediating the (PI3K)/Akt/mTOR pathway. In other words, the consumption of PIs was expedited . Therefore, the lower concentrations of PIs may imply the abnormal activation of the PI3K/AKT pathway in MDR cells.…”