Serum untargeted lipidomics by UHPLC-ESI-HRMS aids the biomarker discovery of colorectal adenoma

Abstract

Background Colorectal adenoma (CA) is an important precancerous lesion and early screening target of colorectal cancer (CRC). Lipids with numerous physiological functions are proved to be involved in the development of CRC. However, there is no lipidomic study with large-scale serum samples on diagnostic biomarkers for CA. Methods The serum lipidomics of CA patients (n = 50) and normal control (NR) (n = 50) was performed by ultra high performance liquid chromatography-high resolution mass spectrometry with electrospray ionization (UHPLC-ESI-HRMS). Univariate and multivariate statistical analyses were utilized to screen the differential lipids between groups, and combining the constituent ratio analysis and diagnostic efficiency evaluation by receiver operating characteristic (ROC) curve disclosed the potential mechanism and biomarkers for CA. Results There were obvious differences in serum lipid profiles between CA and NR groups. Totally, 79 differential lipids were selected by criterion of P < 0.05 and fold change > 1.5 or < 0.67. Triacylglycerols (TAGs) and phosphatidylcholines (PCs) were the major differential lipids with ratio > 60%, indicating these two lipid metabolic pathways showed evident disequilibrium, which could contribute to CA formation. Of them, 12 differential lipids had good diagnostic ability as candidate biomarkers for CA (AUC ≥ 0.900) by ROC analysis. Conclusions To our knowledge, this is the first attempt to profile serum lipidomics and explore lipid biomarkers of CA to help early screening of CRC. 12 differential lipids are obtained to act as potential diagnostic markers of CA. PCs and fatty acids were the main dysregulated biomarkers for CA in serum.

Serum lipidomics reveals novel biomarkers by UHPLC-HRMS to assist the discrimination between colorectal adenoma and cancer

“…In the plasma metabolomics, 48 differential metabolites mainly including LPCs and PCs are uncovered between CA and CRC, and the levels of them are down-regulated in CRC (35). In our previous study, PCs are predominant components of differential lipid species between CA and normal control (NR), and which are signi cantly reduced in CA, indicating that abnormal metabolism of PC should contribute to the formation of CA (24). Similarly, the present study found that PCs were notably downregulated in CRC patients compared with CA patients (Table 2, Figs.…”

“…Lipid metabolism is a complex process involving lipid uptake, transport, synthesis, and degradation (26). Accumulating studies have shown that dysregulated lipid metabolism causes the abnormalities of membrane composition, protein distribution and functions, gene expression and cellular functions, and further leads to the occurrence and development of many cancers, such as breast, prostate, ovarian, and colorectal (24)(25)(26). Meanwhile, dyslipidemia has been recognized as an important risk factor of CA and CRC (24,27).…”

“…It is well known that PCs are the most abundant glycerophospholipids in eukaryotic membranes, which are related to tumor cell proliferation and signal transduction (25,28). Metabolic disorders of PCs have been found in various tumors, and some PCs have great potential as tumor biomarkers (24,25,29).…”

“…(2) Patients were not attacked with severe metabolic or hematologic diseases or malignancy. The collection procedure of serum samples is consistent with our previous study (24). All whole-blood samples were taken after an 8-hour fast, left to stand at room temperature for 25 min, and serum was then collected following centrifugation at 5000 rpm/min for 10 min at 4°C.…”

“…The detailed method and parameter settings of lipidomic analysis for human serum samples were referred to our previous study (24). Serum lipidomic analysis was performed using Dionex Ultimate 3000 liquid chromatography system (Sunnyvale, CA, USA) (SN: 7254012) coupled to Thermo Fisher Q Exactive Orbitrap mass spectrometry system (Waltham, MA, USA) (SN: SN02386L), operated in positive and negative ionization modes, respectively.…”