Identifying metabolic alterations in newly diagnosed small cell lung cancer patients
Pedersen, Shona; Hansen, Joachim Bavnhøj; Maltesen, Raluca Georgiana; Szejniuk, Weronica Maria; Andreassen, Trygve; Falkmer, Ursula; Kristensen, Søren Risom
Peer reviewed, Journal article
Published version
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Date
2021Metadata
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Original version
10.1016/j.metop.2021.100127Abstract
Background
Small cell lung cancer (SCLC) is a malignant disease with poor prognosis. At the time of diagnosis most patients are already in a metastatic stage. Current diagnosis is based on imaging, histopathology, and immunohistochemistry, but no blood-based biomarkers have yet proven to be clinically successful for diagnosis and screening. The precise mechanisms of SCLC are not fully understood, however, several genetic mutations, protein and metabolic aberrations have been described. We aim at identifying metabolite alterations related to SCLC and to expand our knowledge relating to this aggressive cancer.
Methods
A total of 30 serum samples of patients with SCLC, collected at the time of diagnosis, and 25 samples of healthy controls were included in this study. The samples were analyzed with nuclear magnetic resonance spectroscopy. Multivariate, univariate and pathways analyses were performed.
Results
Several metabolites were identified to be altered in the pre-treatment serum samples of small-cell lung cancer patients compared to healthy individuals. Metabolites involved in tricarboxylic acid cycle (succinate: fold change (FC) = 2.4, p = 0.068), lipid metabolism (LDL triglyceride: FC = 1.3, p = 0.001; LDL-1 triglyceride: FC = 1.3, p = 0.012; LDL-2 triglyceride: FC = 1.4, p = 0.009; LDL-6 triglyceride: FC = 1.5, p < 0.001; LDL-4 cholesterol: FC = 0.5, p = 0.007; HDL-3 free cholesterol: FC = 0.7, p = 0.002; HDL-4 cholesterol FC = 0.8, p < 0.001; HDL-4 apolipoprotein-A1: FC = 0.8, p = 0.005; HDL-4 apolipoprotein-A2: FC ≥ 0.7, p ≤ 0.001), amino acids (glutamic acid: FC = 1.7, p < 0.001; glutamine: FC = 0.9, p = 0.007, leucine: FC = 0.8, p < 0.001; isoleucine: FC = 0.8, p = 0.016; valine: FC = 0.9, p = 0.032; lysine: FC = 0.8, p = 0.004; methionine: FC = 0.8, p < 0.001; tyrosine: FC = 0.7, p = 0.002; creatine: FC = 0.9, p = 0.030), and ketone body metabolism (3-hydroxybutyric acid FC = 2.5, p < 0.001; acetone FC = 1.6, p < 0.001), among other, were found deranged in SCLC.
Conclusions
This study provides novel insight into the metabolic disturbances in pre-treatment SCLC patients, expanding our molecular understanding of this malignant disease.