Lung cancer is by far the leading cause of cancer death. Metabolomic studies have highlighted that both tumor progression and limited curative treatment options are partly due to dysregulated glucose metabolism and its associated signaling pathways. In our previous studies, we identified caspase-4 as a novel diagnostic tool for non-small cell lung cancer (NSCLC). Here, we analyzed the metabolomic profile of both plasma and tumor tissues of NSCLC patients stratified as caspase-4 positive or negative. We found that circulating caspase-4 was correlated to LDH. However, this effect was not observed in caspase-4 positive tumor tissues, where instead, fatty acid biosynthesis was favoured in that the malonic acid and the palmitic acid were higher than in non-cancerous and caspase-4 negative tissues. The glycolytic pathway in caspase-4 positive NSCLC tissues was bypassed by the malonic acid-dependent lipogenesis. On the other hand, the dysregulated glucose metabolism was regulated by a higher presence of succinate dehydrogenase (SDHA) and by the gluconeogenic valine which favoured Krebs' cycle. In conclusion, we found that the recently identified caspase-4 positive subpopulation of NSCLC patients is characterized by a lipidomic profile accompanied by alternative pathways to guarantee glucose metabolism in favour of tumor cell proliferation.
Background: One of the most challenging aspects related to Covid-19 is to establish which are the characteristics that may explain clinical variability among patients. To achieve this objective, we compared serum metabolomic profiles of asymptomatic SARS-CoV-2 carriers to patients affected by mild and severe symptoms.Methods: All subjects underwent quantitative assays for anti-SARS-CoV-2 antibody detection. Serum samples for metabolomic analysis were obtained from 109 healthy controls; 15 seroconverted, asymptomatic subjects (AS); 16 Covid-19 patients with mild symptomatology (MI) and 12 patients with severe symptomatology (SE). Metabolites were identified using Mass Spectrometry coupled to Gas Chromatography. Uni- and multivariate approaches were used to select the most relevant metabolites. Results: Anti SARS-CoV-2 IgG showed an increasing trend from controls to asymptomatic and mild severity patients. Tyrosine, phenylalanine, acetoacetate and fumarate showed a decreased concentration in MI compared to both CTRL and AS subjects; on the contrary, mandelic acid showed an increased concertation. The shortest route among these metabolites resulted the Tyrosine metabolism. Aspartic acid, alanine, isoleucine, valine and proline were decreased in MI patients, while methionine and oxo-leucine resulted increased. An increased concertation of fatty acids lauric and myristic acid, phospholipids (phosphatidyl myo-inositol and lyso-phosphatidyl inositol) and histamine were recorded in MI and SE. Conclusion: The reported metabolite levels could be explained by an increase production of L-DOPA, resulting in a following increased production of noradrenaline and adrenaline that could, at least partially, explain the different clinical presentation of the infection.
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