Identification of Plasma Metabolomic Profiling for Diagnosis of Esophageal Squamous-Cell Carcinoma Using an UPLC/TOF/MS Platform

Abstract

Epidemiological studies indicated that esophageal squamous-cell carcinoma (ESCC) is still one of the most common causes of cancer incidence in the world. Searching for valuable markers including circulating endogenous metabolites associated with the risk of esophageal cancer, is extremely important A comparative metabolomics study was performed by using ultraperformance liquid chromatography-electrospray ionization-accurate mass time-of-flight mass spectrometry to analyze 53 pairs of plasma samples from ESCC patients and healthy controls recruited in Huaian, China. The result identified a metabolomic profiling of plasma including 25 upregulated metabolites and five downregulated metabolites, for early diagnosis of ESCC. With a database-based verification protocol, 11 molecules were identified, and six upregulated molecules of interest in ESCC were found to belong to phospholipids as follows: phosphatidylserine, phosphatidic acid, phosphatidyl choline, phosphatidylinositol, phosphatidyl ethanolamine, and sphinganine 1-phosphate. Clinical estimation of metabolic biomarkers through hierarchical cluster analysis in plasma samples from 17 ESCC patients and 29 healthy volunteers indicated that the present metabolite profile could distinguish ESCC patients from healthy individuals. The cluster of aberrant expression of these metabolites in ESCC indicates the critical role of phospholipid metabolism in the oncogenesis of ESCC and suggests its potential ability to assess the risk of ESCC development in addition to currently used risk factors.

Identification of Serum Markers of Esophageal Adenocarcinoma by Global and Targeted Metabolic Profiling

“…A previous metabolomics study of EAC serum specimens using a case-control design also included cases with Barrett’s esophagus 7, 8 . However, that study did not include an external validation and the sample sizes were small.…”

“…To date, metabolomic studies on EC included profiling serum and urine samples to identify differential metabolite markers between patients and controls 5,6 and potentially useful metabolic profiles for diagnosis of either SCC 7 and EAC 8 . However, no external validation was included and no insight into biochemical processes altered in EC was provided.…”

Advances in Lipidomics for Cancer Biomarkers Discovery

“…PS, PA, PC, PI, PE and sphinganine 1-phosphate were overexpressed in cancer patient plasma compared to healthy controls. This demonstrated the critical role of PLs in the SCC oncogenesis; therefore, the identification of novel biomarkers could be an important strategy to reaching an early diagnosis that could improve clinical outcome [106]. Biomarkers’ diagnostic value has been recently evaluated by Uchiyama and colleagues, with the intention of distinguishing biomolecule distributions through IMS, in 11 signals between neoplasm and stromal regions.…”

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

“…Metabolomics, the global semi-quantitative assessment of endogenous small molecule metabolites within a biological system, has been successfully utilized in cancer biomarker discovery (Spratlin et al 2009;Zhang et al 2013, b;Ke et al 2015). Up to now, a few ESCC metabolomics studies has been reported using specimen of serum (Djukovic et al 2010;Zhang et al 2011;Ikeda et al 2012;Zhang et al 2012aZhang et al , b, 2013Jin et al 2014;Mir et al 2015), plasma (Hasim et al 2012;Liu et al 2013;Xu et al 2013;Ma et al 2014), urine (Davis et al 2012;Hasim et al 2012), tissue (Wu et al 2009;Yakoub et al 2010;Wang et al 2013;Yang et al 2013;Lynam-Lennon et al 2014) or gastric content (Kumar et al 2012), and conducted on mass spectrometry (MS) and nuclear magnetic resonance (NMR) platforms. These studies revealed significantly perturbed metabolic expression in ESCC patients compared with healthy controls.…”