Serum metabolomics for early diagnosis of esophageal squamous cell carcinoma by UHPLC-QTOF/MS

Abstract

Introduction Previous metabolomics studies have revealed perturbed metabolic signatures in esophageal squamous cell carcinoma (ESCC) patients, however, most of these studies included mainly late-staged ESCC patients due to the difficulties of collecting the early-staged samples from asymptotic ESCC subjects. Objectives This study aims to explore the early-staged ESCC metabolic signatures and potential of serum metabolomics to diagnose ESCC at early stages. Methods Serum samples of 97 ESCC patients (stage 0, 39 cases; stage I, 17 cases; stage II, 11 cases, stage III, 30 cases) and 105 healthy controls (HC) were enrolled and randomly separated into training data (77 ESCCs, 84 HCs) and validation data (20 ESCCs, 21 HCs). Untargeted metabolomics was performed to identify ESCC-related metabolic signatures. ResultsThe global metabolomics profiles could clearly distinguish ESCC from HC in training data. 16 ascertained metabolites were found to be disturbed in the metabolic pathways characterized by dysregulated fatty acid biosynthesis, glycerophospholipid metabolism, choline metabolism in cancer and linoleic acid metabolism. The AUC value in validation data was 0.895, with sensitivity 85.0 % and specificity 90.5 %. Good diagnostic performances were also achieved for early stage ESCC, with the values of area under the curve (AUC) 0.881 for the ESCC patients in both stage 0 and I-II. In addition, six metabolites were found to discriminate ESCC stages. Among them, three biomarkers, dodecanoic acid, LysoPA(18:1), and LysoPC(14:0), exhibited clear trend for ESCC progression. Conclusion These findings suggest serum metabolomics, performed in a minimally noninvasive and convenient manner, may possess great potential for early diagnosis of ESCC patients.

Untargeted Metabolomics Analysis of Esophageal Squamous Cell Carcinoma Discovers Dysregulated Metabolic Pathways and Potential Diagnostic Biomarkers

“…This pathway, which contains both LA and ALA, is vital for normal physiological function, cellular function and signaling, and the immune response [36]. A series of studies has shown that dysregulation of LA metabolism takes place in a variety of malignant diseases [17,24,37]. However, the separate roles of the LA and ALA in ESCC risk remain unclear and our understanding of them incomplete.…”

“…Mayerle et al [16] recruited patients for a large-scale study to differentiate pancreatic ductal adenocarcinoma from chronic pancreatitis, achieving high accuracy. In order to elucidate the mechanisms of ESCC onset and discover novel biomarkers, Wang et al [17] analyzed a relatively large number of early-stage ESCCs by serum LC-MS-based metabolomics. Moreover, Xu et al [18] discovered a series of potential biomarkers for ESCC diagnostic and therapeutic purposes.…”

Metabolic Biomarkers of Squamous Cell Carcinoma of the Aerodigestive Tract: A Systematic Review and Quality Assessment

“…All studies were Phase I biomarker discovery studies. Of the 30 included studies, 18 were from Asia and the Far East [8,9,[11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26], seven from Europe [27][28][29][30][31][32][33], three from North America [34][35][36], and two from the Middle East [37,38]. ASCC tumour sites identified were the head and neck (n = 17), oesophageal (n = 8), and lung (n = 5).…”

Enhancement of bile resistance by maltodextrin supplementation in Lactobacillus plantarum Lp‐115

“…LC‐MS/MS analyses (Wang et al . ) were performed using an UHPLC system (1290; Agilent Technologies, Palo Alto, CA, USA) with a UPLC HSS T3 column (1·7 μ m × 2·1 mm × 100 mm; Waters, Milford, MA, USA) coupled to Q Exactive (Orbitrap MS; Thermo, Waltham, MA, USA). MS raw data (.d) files were converted to the mzML format using ProteoWizard, and processed by R package xcms (ver.…”

“…After homogenization for three times, it was incubated for 1 h at À20°C to precipitate proteins and then centrifuged at 17 000 g for 15 min at 4°C to get the resulting supernatants. LC-MS/MS analyses (Wang et al 2016) were performed using an UHPLC system (1290; Agilent Technologies, Palo Alto, CA, USA) with a UPLC HSS T3 column (1Á7 lm 9 2Á1 mm 9 100 mm; Waters, Milford, MA, USA) coupled to Q Exactive (Orbitrap MS; Thermo, Waltham, MA, USA). MS raw data (.d) files were converted to the mzML format using ProteoWizard, and processed by R package XCMS (ver.…”