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

• Published in: Molecular oncology 2018-10, Vol.12 (10), p.1778-1796
• Main Authors: Moreno, Paula, Jiménez‐Jiménez, Carla, Garrido‐Rodríguez, Martín, Calderón‐Santiago, Mónica, Molina, Susana, Lara‐Chica, Maribel, Priego‐Capote, Feliciano, Salvatierra, Ángel, Muñoz, Eduardo, Calzado, Marco A.
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Aged; Biological markers; Biomarkers; Biomarkers, Tumor - metabolism; Cancer therapies; Chromatography; Discriminant analysis; Female; Gene expression; Gene Expression Regulation, Neoplastic; Genetic analysis; Glucose - metabolism; Glutathione - metabolism; Health aspects; Humans; Hydroxymethyl and Formyl Transferases - genetics; Hydroxymethyl and Formyl Transferases - metabolism; Ions; Lung cancer; Lung carcinoma; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - therapy; Male; Mass spectrometry; Mass spectroscopy; Metabolism; Metabolites; Metabolome; Metabolomics; Metabolomics - methods; Middle Aged; Multienzyme Complexes - genetics; Multienzyme Complexes - metabolism; Nucleotide Deaminases - genetics; Nucleotide Deaminases - metabolism; nucleotides; Nucleotides - metabolism; Oxidative Stress; Patients; Physiological aspects; Polyamines - metabolism; Principal components analysis; Purines - metabolism; Quality control; ROC Curve; Scientific imaging; Therapeutic applications; Tumors; Urine
• ISSN: 1574-7891; 1878-0261
• DOI: 10.1002/1878-0261.12369

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. The aim of this study has been the complete analysis of the metabolic profile of a relevant number of lung cancer tissues, including the most important histological subtypes. The obtained data prove the presence of biochemical changes at tissue level, which can be useful to identify biomarkers and increase the knowledge of the metabolic reprogramming developed during tumorigenesis.