Systemic Metabolomic Changes in Blood Samples of Lung Cancer Patients Identified by Gas Chromatography Time-of-Flight Mass Spectrometry.

Lung cancer is a leading cause of cancer deaths worldwide. Metabolic alterations in tumor cells coupled with systemic indicators of the host response to tumor development have the potential to yield blood profiles with clinical utility for diagnosis and monitoring of treatment. We report results from two separate studies using gas chromatography time-of-flight mass spectrometry (GC-TOF MS) to profile metabolites in human blood samples that significantly differ from non-small cell lung cancer (NSCLC) adenocarcinoma and other lung cancer cases. Metabolomic analysis of blood samples from the two studies yielded a total of 437 metabolites, of which 148 were identified as known compounds and 289 identified as unknown compounds. Differential analysis identified 15 known metabolites in one study and 18 in a second study that were statistically different (p-values <0.05). Levels of maltose, palmitic acid, glycerol, ethanolamine, glutamic acid, and lactic acid were increased in cancer samples while amino acids tryptophan, lysine and histidine decreased. Many of the metabolites were found to be significantly different in both studies, suggesting that metabolomics appears to be robust enough to find systemic changes from lung cancer, thus showing the potential of this type of analysis for lung cancer detection

Effects of observed and experimental climate change on terrestrial ecosystems in northern Canada: results from the Canadian IPY program

Published VersionTundra and taiga ecosystems comprise nearly 40 % of the terrestrial landscapes of Canada. These permafrost ecosystems have supported humans for more than 4500 years, and are currently home to ca. 115,000 people, the majority of whom are First Nations, Inuit and Métis. The responses of these ecosystems to the regional warming over the past 30–50 years were the focus of four Canadian IPY projects. Northern residents and researchers reported changes in climate and weather patterns and noted shifts in vegetation and other environmental variables. In forest-tundra areas tree growth and reproductive effort correlated with temperature, but seedling establishment was often hindered by other factors resulting in sitespecific responses. Increased shrub cover has occurred in sites across the Arctic at the plot and landscape scale, and this was supported by results from experimental warming. Experimental warming increased vegetation cover and nutrient availability in most tundra soils; however, resistance to warming was also found. Soil microbial diversity in tundra was no different than in other biomes, although there were shifts in mycorrhizal diversity in warming experiments. All sites measured were sinks for carbon during the growing season with expected seasonal and latitudinal patterns. Modeled responses of a mesic tundra system to climate change showed that the sink status will likely continue for the next 50–100 years, after which these tundra systems will likely become a net source of carbon dioxide to the atmosphere. These IPY studies were the first comprehensive assessment of the state and change in Canadian northern terrestrial ecosystems and showed that the inherent variability in these systems is reflected in their site-specific responses to changes in climate. They also showed the importance of using local traditional knowledge and science, and provided extensive data sets, sites and researchers needed to study and manage the inevitable changes in the Canadian North

Systemic Metabolomic Changes in Blood Samples of Lung Cancer Patients Identified by Gas Chromatography Time-of-Flight Mass Spectrometry

Lung cancer is a leading cause of cancer deaths worldwide. Metabolic alterations in tumor cells coupled with systemic indicators of the host response to tumor development have the potential to yield blood profiles with clinical utility for diagnosis and monitoring of treatment. We report results from two separate studies using gas chromatography time-of-flight mass spectrometry (GC-TOF MS) to profile metabolites in human blood samples that significantly differ from non-small cell lung cancer (NSCLC) adenocarcinoma and other lung cancer cases. Metabolomic analysis of blood samples from the two studies yielded a total of 437 metabolites, of which 148 were identified as known compounds and 289 identified as unknown compounds. Differential analysis identified 15 known metabolites in one study and 18 in a second study that were statistically different (p-values <0.05). Levels of maltose, palmitic acid, glycerol, ethanolamine, glutamic acid, and lactic acid were increased in cancer samples while amino acids tryptophan, lysine and histidine decreased. Many of the metabolites were found to be significantly different in both studies, suggesting that metabolomics appears to be robust enough to find systemic changes from lung cancer, thus showing the potential of this type of analysis for lung cancer detection

Absolute Quantitation of Immunoglobulin G and Its Glycoforms Using Multiple Reaction Monitoring

Studies aimed toward glycan biomarker discovery have focused on glycan characterization by the global profiling of released glycans. Site-specific glycosylation analysis is less developed but may provide new types of biomarkers with higher sensitivity and specificity. Quantitation of peptide-conjugated glycans directly facilitates the differential analysis of distinct glycoforms associated with specific proteins at distinct sites. We have developed a method using MRM to monitor protein glycosylation normalized to absolute protein concentrations to examine quantitative changes in glycosylation at a site-specific level. This new approach provides information regarding both the absolute amount of protein and the site-specific glycosylation profile and will thus be useful to determine if altered glycosylation profiles in serum/plasma are due to a change in protein glycosylation or a change in protein concentration. The remarkable sensitivity and selectivity of MRM enable the detection of low abundance IgG glycopeptides, even when IgG was digested directly in serum with no cleanup prior to the liquid chromatography. Our results show a low limit of detection of 60 amol and a wide dynamic range of 3 orders magnitude for IgG protein quantitation. The results show that IgG glycopeptides can be analyzed directly from serum (without enrichment) and yield more accurate abundances when normalized to the protein content. This report represents the most comprehensive study so far of the use of multiple reaction monitoring for the quantitation of glycoproteins and their glycosylation patterns in biofluids