Lung cancer is the leading cause of cancer deaths in the United States. Patients with early stage lung cancer have the best prognosis with surgical removal of the tumor, but the disease is often asymptomatic until advanced disease develops, and there are no effective blood-based screening methods for early detection of lung cancer in at-risk populations. We have explored the lipid profiles of blood plasma exosomes using ultra high-resolution Fourier transform mass spectrometry (UHR-FTMS) for early detection of the prevalent non-small cell lung cancers (NSCLC). Exosomes are nanovesicles released by various cells and tumor tissues to elicit important biofunctions such as immune modulation and tumor development. Plasma exosomal lipid profiles were acquired from 39 normal and 91 NSCLC subjects (44 early stage and 47 late stage). We have applied two multivariate statistical methods, Random Forest (RF) and Least Absolute Shrinkage and Selection Operator (LASSO) to classify the data. For the RF method, the Gini importance of the assigned lipids was calculated to select 16 lipids with top importance. Using the LASSO method, 7 features were selected based on a grouped LASSO penalty. The Area Under the Receiver Operating Characteristic curve for early and late stage cancer versus normal subjects using the selected lipid features was 0.85 and 0.88 for RF and 0.79 and 0.77 for LASSO, respectively. These results show the value of RF and LASSO for metabolomics data-based biomarker development, which provide robust an independent classifiers with sparse data sets. Application of LASSO and Random Forests identifies lipid features that successfully distinguish early stage lung cancer patient from healthy individuals.
Many studies on yeast metabolism are focused on its response to specific stress conditions because the results can be extended to the human medical issues. Most of those works have been accomplished through functional genomics studies. However, these changes may not show a linear correlation with protein or metabolite levels. For many organisms including yeast, the number of metabolites is far fewer than that of genes or gene products. Thus, metabolic profiling can provide a simpler yet efficient snapshot of the system's physiology. Metabolites of Saccharomyces cerevisiae under various stresses were analyzed and compared with those under the normal, unstressed growth conditions by two-dimensional NMR spectroscopy. At least 31 metabolites were identified for most of the samples. The levels of many identified metabolites showed significant increase or decrease depending on the nature of the stress. The statistical analysis produced a holistic view: different stresses were clustered and isolated from one another with the exception of high pH, heat, and oxidative stresses. This work could provide a link between the metabolite profiles and mRNA or protein profiles under representative and well-studied stress conditions.
Metabolites of colorectal cancer tissues from 12 patients were analyzed and compared with those of the normal tissues by two-dimensional NMR spectroscopy. NMR data were analyzed with the help of the metabolome database and the statistics software. Cancerous tissues showed significantly altered metabolic profiles as compared to the normal tissues. Among such metabolites, the concentrations of taurine, glutamate, choline were notably increased in the cancerous tissues of most patients, and those of glucose, malate, and glycerol were decreased. Changes in individual metabolites varied significantly from patient to patient, but the combination of such changes could be used to distinguish cancerous tissues from normal ones, which could be done by PCA analysis. The traditional chemometric analysis was also performed using AMIX software. By comparing those two results, the analysis via 1 H-13 C HSQC spectra proved to be more robust and effective in assessing and classifying global metabolic profiles of the colorectal tissues.
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