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Metabolomic profiling of human lung tumor tissues - nucleotide metabolism as a candidate for therapeutic interventions and biomarkers.

ABSTRACT: Although metabolomics has attracted considerable attention in the field of lung cancer (LC) detection and management, only a very limited number of works have applied it to tissues. As such, the aim of this study was the thorough analysis of metabolic profiles of relevant LC tissues, including the most important histological subtypes (adenocarcinoma and squamous cell lung carcinoma). Mass spectrometry-based metabolomics, along with genetic expression and histological analyses, were performed as part of this study, the widest to date, to identify metabolic alterations in tumors of the most relevant histological subtypes in lung. A total of 136 lung tissue samples were analyzed and 851 metabolites were identified through metabolomic analysis. Our data show the existence of a clear metabolic alteration not only between tumor vs. nonmalignant tissue in each patient, but also inherently intrinsic changes in both AC and SCC. Significant changes were observed in the most relevant biochemical pathways, and nucleotide metabolism showed an important number of metabolites with high predictive capability values. The present study provides a detailed analysis of the metabolomic changes taking place in relevant biochemical pathways of the most important histological subtypes of LC, which can be used as biomarkers and also to identify novel targets.

SUBMITTER: Moreno P

PROVIDER: S-EPMC6165994 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Metabolomic profiling of human lung tumor tissues - nucleotide metabolism as a candidate for therapeutic interventions and biomarkers.

Moreno Paula P Jiménez-Jiménez Carla C Garrido-Rodríguez Martín M Calderón-Santiago Mónica M Molina Susana S Lara-Chica Maribel M Priego-Capote Feliciano F Salvatierra Ángel Á Muñoz Eduardo E Calzado Marco A MA

Molecular oncology 20180913 10

Although metabolomics has attracted considerable attention in the field of lung cancer (LC) detection and management, only a very limited number of works have applied it to tissues. As such, the aim of this study was the thorough analysis of metabolic profiles of relevant LC tissues, including the most important histological subtypes (adenocarcinoma and squamous cell lung carcinoma). Mass spectrometry-based metabolomics, along with genetic expression and histological analyses, were performed as ...[more]

PMID: 30099851

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Project description:Adenocarcinoma, a type of non-small cell lung cancer, is the most frequently diagnosed lung cancer and the leading cause of lung cancer mortality in the United States. It is well documented that biochemical changes occur early in the transition from normal to cancer cells, but the extent to which these alterations affect tumorigenesis in adenocarcinoma remains largely unknown. Herein, we describe the application of mass spectrometry and multivariate statistical analysis in one of the largest biomarker research studies to date aimed at distinguishing metabolic differences between malignant and nonmalignant lung tissue. Gas chromatography time-of-flight mass spectrometry was used to measure 462 metabolites in 39 malignant and nonmalignant lung tissue pairs from current or former smokers with early stage (stage IA-IB) adenocarcinoma. Statistical mixed effects models, orthogonal partial least squares discriminant analysis and network integration, were used to identify key cancer-associated metabolic perturbations in adenocarcinoma compared with nonmalignant tissue. Cancer-associated biochemical alterations were characterized by (i) decreased glucose levels, consistent with the Warburg effect, (ii) changes in cellular redox status highlighted by elevations in cysteine and antioxidants, alpha- and gamma-tocopherol, (iii) elevations in nucleotide metabolites 5,6-dihydrouracil and xanthine suggestive of increased dihydropyrimidine dehydrogenase and xanthine oxidoreductase activity, (iv) increased 5'-deoxy-5'-methylthioadenosine levels indicative of reduced purine salvage and increased de novo purine synthesis, and (v) coordinated elevations in glutamate and UDP-N-acetylglucosamine suggesting increased protein glycosylation. The present study revealed distinct metabolic perturbations associated with early stage lung adenocarcinoma, which may provide candidate molecular targets for personalizing therapeutic interventions and treatment efficacy monitoring.

Dataset Information

Metabolomic profiling of human lung tumor tissues - nucleotide metabolism as a candidate for therapeutic interventions and biomarkers.

Publications

Metabolomic profiling of human lung tumor tissues - nucleotide metabolism as a candidate for therapeutic interventions and biomarkers.

Similar Datasets

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