Juzheng Huang

Selected Ion Flow Tube Mass Spectrometry Analysis of Exhaled Breath for Volatile Organic Compound Profiling of Esophago-Gastric Cancer

Exhaled breath analysis of volatile organic compounds (VOCs) has great potential in terms of disease diagnosis and measuring physiological response to treatment. In this study, selected ion flow tube mass spectrometry (SIFT-MS) has been applied for the quantification of VOCs in the exhaled breath from 3 groups of patients, viz., those with esophago-gastric cancer, noncancer diseases of the upper gastro-intestinal tract, and a healthy upper gastrointestinal tract cohort. A total of 17 VOCs have been investigated in this study. The concentrations of 4 VOCs, hexanoic acid, phenol, methyl phenol, and ethyl phenol, were found to be significantly different between cancer and positive control groups using the Mann-Whitney U test. Receiver operating characteristics (ROC) analysis was applied for a combination of 4 VOCs (hexanoic acid, phenol, methyl phenol, and ethyl phenol) to discriminate the esophago-gastric cancer cohort from positive controls. The integrated area under the ROC curve (AUC) is 0.91. The results highlight the potential of VOC profiling as a noninvasive test to identify those with esophago-gastric cancer.

Selected ion flow tube mass spectrometry analysis of volatile metabolites in urine headspace for the profiling of gastro-esophageal cancer.

Urine is considered an ideal biofluid for clinical investigation because it is obtained noninvasively and relatively large volumes are easily acquired. In this study, selected ion flow tube mass spectrometry (SIFT-MS) has been applied for the quantification of volatile organic compounds (VOCs) in the headspace vapor of urine samples, which were retrieved from three groups of patients with gastro-esophageal cancer, noncancer diseases of the upper gastro-intestinal tract, and a healthy cohort. Eleven VOCs have been investigated in this study. The concentrations of seven VOCs-acetaldehyde, acetone, acetic acid, hexanoic acid, hydrogen sulfide, methanol, and phenol-were found to be significantly different between cancer, positive control, and healthy groups using the Kruskal-Wallis test. The concentrations of acetaldehyde, acetone, acetic acid, hexanoic acid, hydrogen sulfide, and methanol were increased in the cancer cohort compared with healthy controls while the concentration of phenol decreased. The differences in the concentrations of ethanol, propanol, methyl phenol, and ethyl phenol were not significant between cancer and control groups. Receiver operating characteristics (ROC) analysis was applied for a combination of six VOCs (acetaldehyde, acetone, acetic acid, hexanoic acid, hydrogen sulfide, and methanol) to discriminate cancer patients from noncancer controls. The integrated area under ROC curve is 0.904. This result indicates that VOC profiling may be suitable in identifying those at high risk of gastro-esophageal cancer. Therefore, further investigations should be undertaken to assess the potential for VOC profiling as a new screening test in gastro-esophageal cancer.

Selected ion flow tube-MS analysis of headspace vapor from gastric content for the diagnosis of gastro-esophageal cancer.

Gastric content is a complex biofluid within the human stomach which has an important role in digestive processes. It is believed that gastric content may be a contributory factor in the development of upper gastro-intestinal diseases. In this work, selected ion flow tube mass spectrometry (SIFT-MS) has been applied to the quantification of volatile organic compounds (VOCs) in the headspace vapor of gastric content samples, which were retrieved from three groups of patients, including those with gastro-esophageal cancer, noncancer diseases of the upper gastro-intestinal tract, and a healthy cohort. Twelve VOCs have been investigated in this study; the following 7 VOCs, acetone, formaldehyde, acetaldehyde, hexanoic acid, hydrogen sulphide, hydrogen cyanide, and methyl phenol, were found to be significantly different between cancer and healthy groups by the Mann-Whitney U test. Receiver operating characteristics (ROC) analysis was applied for the combined VOCs of acetaldehyde, formaldehyde, hydrogen sulphide, and methyl phenol to discriminate cancer patients from healthy controls. The area under the curve (AUC) was 0.9. This result raises the prospect that a VOC profile rather than a single biomarker may be preferable in the molecular-orientated diagnosis of gastro-oseophageal cancer, and this warrants further investigation to assess its potential application as a new diagnostic test.

Mass Spectrometric Analysis of Exhaled Breath for the Identification of Volatile Organic Compound Biomarkers in Esophageal and Gastric Adenocarcinoma

Objective: The present study assessed whether exhaled breath analysis using Selected Ion Flow Tube Mass Spectrometry could distinguish esophageal and gastric adenocarcinoma from noncancer controls. Background: The majority of patients with upper gastrointestinal cancer present with advanced disease, resulting in poor long-term survival rates. Novel methods are needed to diagnose potentially curable upper gastrointestinal malignancies. Methods: A Profile-3 Selected Ion Flow Tube Mass Spectrometry instrument was used for analysis of volatile organic compounds (VOCs) within exhaled breath samples. All study participants had undergone upper gastrointestinal endoscopy on the day of breath sampling. Receiver operating characteristic analysis and a diagnostic risk prediction model were used to assess the discriminatory accuracy of the identified VOCs. Results: Exhaled breath samples were analyzed from 81 patients with esophageal (N = 48) or gastric adenocarcinoma (N = 33) and 129 controls including Barretts metaplasia (N = 16), benign upper gastrointestinal diseases (N = 62), or a normal upper gastrointestinal tract (N = 51). Twelve VOCs—pentanoic acid, hexanoic acid, phenol, methyl phenol, ethyl phenol, butanal, pentanal, hexanal, heptanal, octanal, nonanal, and decanal—were present at significantly higher concentrations (P < 0.05) in the cancer groups than in the noncancer controls. The area under the ROC curve using these significant VOCs to discriminate esophageal and gastric adenocarcinoma from those with normal upper gastrointestinal tracts was 0.97 and 0.98, respectively. The area under the ROC curve for the model and validation subsets of the diagnostic prediction model was 0.92 ± 0.01 and 0.87 ± 0.03, respectively. Conclusions: Distinct exhaled breath VOC profiles can distinguish patients with esophageal and gastric adenocarcinoma from noncancer controls.

In Vivo Endoscopic Tissue Identification by Rapid Evaporative Ionization Mass Spectrometry (REIMS)

Gastrointestinal cancers are a leading cause of mortality, accounting for 23 % of cancer-related deaths worldwide. In order to improve outcomes from these cancers, novel tissue characterization methods are needed to facilitate accurate diagnosis. Rapid evaporative ionization mass spectrometry (REIMS) is a technique developed for the in vivo classification of human tissue through mass spectrometric analysis of aerosols released during electrosurgical dissection. This ionization technique was further developed by utilizing surface induced dissociation and was integrated with an endoscopic polypectomy snare to allow in vivo analysis of the gastrointestinal tract. We tested the classification performance of this novel endoscopic REIMS method in vivo. It was shown to be capable of differentiating between healthy layers of the intestinal wall, cancer, and adenomatous polyps based on the REIMS fingerprint of each tissue type in vivo.

Metabolomic profiling of oesophago-gastric cancer: A systematic review

AIMS This review aims to identify metabolomic biomarkers of oesophago-gastric (OG) cancer in human biological samples, and to discuss the dominant metabolic pathways associated with the observed changes. METHODS A systematic review of the literature, up to and including 9th November 2012, was conducted for experimental studies investigating the metabolomic profile of human biological samples from patients with OG cancer compared to a control group. Inclusion criteria for analytical platforms were mass spectrometry or nuclear magnetic resonance spectroscopy. The QUADAS-2 tool was used to assess the quality of the included studies. RESULTS Twenty studies met the inclusion criteria and samples utilised for metabolomic analysis included tissue (n = 11), serum (n = 8), urine (n = 1) and gastric content (n = 1). Several metabolites of glycolysis, the tricarboxylic acid cycle, anaerobic respiration and protein/lipid metabolism were found to be significantly different between cancer and control samples. Lactate and fumurate were the most commonly recognised biomarkers of OG cancer related to cellular respiration. Valine, glutamine and glutamate were the most commonly identified amino acid biomarkers. Products of lipid metabolism including saturated and un-saturated free fatty acids, ketones and aldehydes and triacylglycerides were also identified as biomarkers of OG cancer. Unclear risk of bias for patient selection was reported for the majority of studies due to the lack of clarity regarding patient recruitment. CONCLUSION The application of metabolomics for biomarker detection in OG cancer presents new opportunities for the purposes of screening and therapeutic monitoring. Future studies should provide clear details of patient selection and develop metabolite assays suitable for progress beyond phase 1 pre-clinical exploratory studies.

Repeatability and reproducibility of desorption electrospray ionization-mass spectrometry (DESI-MS) for the imaging analysis of human cancer tissue: a gateway for clinical applications

In this study, we aim to demonstrate the repeatability and reproducibility of DESI-MS for the imaging analysis of human cancer tissue using a set of optimal geometric and electrospray solvent parameters. Oesophageal cancer tissue was retrieved from four quadrants of a freshly removed tumor specimen, snap frozen, cryo-sectioned and mounted on glass slides for DESI-MS image acquisition. Prior to assessing precision, optimal geometric and electrospray solvent parameters were determined to maximize the number of detected lipid species and associated Total Ion Count (TIC). The same settings were utilized for all subsequent experiments. Repeatability measurements were performed using the same instrument, by the same operator on a total of 16 tissue sections (four from each quadrant of the tumor). Reproducibility measurements were determined in a different laboratory, on a separate DESI-MS platform and by an independent operator on 4 sections of one quadrant and compared to the corresponding measurements made for the repeatability experiments. The mean ± SD CV of lipid ion intensities was found to be 22 ± 7% and 18 ± 8% as measures of repeatability and reproducibility, respectively. In conclusion, DESI-MS has acceptable levels of reproducibility for the analysis of lipids in human cancer tissue and is suitable for the purposes of clinical research and diagnostics.

Analysis of Exhaled Breath Volatile Organic Compounds in Inflammatory Bowel Disease: A Pilot Study

BACKGROUND AND AIMS Distinguishing between the inflammatory bowel diseases [IBD], Crohns disease [CD] and ulcerative colitis [UC], is important for determining management and prognosis. Selected ion flow tube mass spectrometry [SIFT-MS] may be used to analyse volatile organic compounds [VOCs] in exhaled breath: these may be altered in disease states, and distinguishing breath VOC profiles can be identified. The aim of this pilot study was to identify, quantify, and analyse VOCs present in the breath of IBD patients and controls, potentially providing insights into disease pathogenesis and complementing current diagnostic algorithms. METHODS SIFT-MS breath profiling of 56 individuals [20 UC, 18 CD, and 18 healthy controls] was undertaken. Multivariate analysis included principal components analysis and partial least squares discriminant analysis with orthogonal signal correction [OSC-PLS-DA]. Receiver operating characteristic [ROC] analysis was performed for each comparative analysis using statistically significant VOCs. RESULTS OSC-PLS-DA modelling was able to distinguish both CD and UC from healthy controls and from one other with good sensitivity and specificity. ROC analysis using combinations of statistically significant VOCs [dimethyl sulphide, hydrogen sulphide, hydrogen cyanide, ammonia, butanal, and nonanal] gave integrated areas under the curve of 0.86 [CD vs healthy controls], 0.74 [UC vs healthy controls], and 0.83 [CD vs UC]. CONCLUSIONS Exhaled breath VOC profiling was able to distinguish IBD patients from controls, as well as to separate UC from CD, using both multivariate and univariate statistical techniques.

A Comparison of DESI-MS and LC-MS for the Lipidomic Profiling of Human Cancer Tissue

AbstractIn this study, we make a direct comparison between desorption electrospray ionization-mass spectrometry (DESI-MS) and ultraperformance liquid chromatography-electrospray ionization-mass spectrometry (UPLC-ESI-MS) platforms for the profiling of glycerophospholipid (GPL) species in esophageal cancer tissue. In particular, we studied the similarities and differences in the range of GPLs detected and the congruency of their relative abundances as detected by each analytical platform. The main differences between mass spectra of the two modalities were found to be associated with the variance in adduct formation of common GPLs, rather than the presence of different GPL species. Phosphatidylcholines as formate adducts in UPLC-ESI-MS accounted for the majority of differences in negative ion mode and alkali metal adducts of phosphatidylcholines in DESI-MS for positive ion mode. Comparison of the relative abundance of GPLs, normalized to a common peak, revealed a correlation coefficient of 0.70 (P < 0.001). The GPL profile detected by DESI-MS is congruent to UPLC-ESI-MS, which reaffirms the role of DESI-MS for lipidomic profiling and a potential premise for quantification. Graphical Abstractᇵ

Exhaled breath acetone for therapeutic monitoring in pneumonia using selected ion flow tube mass spectrometry (SIFT-MS)

Exhaled breath analysis of volatile organic compounds (VOCs) has great potential in terms of measuring physiological response to treatment. Exhaled breath acetone was measured in patients with community acquired pneumonia for the duration of their in-hospital treatment using Selected Ion Flow Tube-Mass Spectrometry (SIFT-MS). A positive correlation was observed between exhaled breath acetone concentrations and same-day serum C-reactive protein (CRP) levels. Exhaled breath acetone concentrations and CRP levels decreased in the range of 76–90% and 67–80%, respectively, from the day of admission to the day of discharge. This proof of concept study demonstrates the potential of SIFT-MS exhaled breath analysis as a non-invasive tool for clinical therapeutic monitoring.