Abstract
Lung cancer causes more deaths in men and women than any other cancer related disease. Currently, few effective strategies exist to predict how patients will respond to treatment. We evaluated the serum metabolomic profiles of 25 lung cancer patients undergoing chemotherapy ± radiation to evaluate the feasibility of metabolites as temporal biomarkers of clinical outcomes. Serial serum specimens collected prospectively from lung cancer patients were analyzed using both nuclear magnetic resonance (1H-NMR) spectroscopy and gas chromatography mass spectrometry (GC–MS). Multivariate statistical analysis consisted of unsupervised principal component analysis or orthogonal partial least squares discriminant analysis with significance assessed using a cross-validated ANOVA. The metabolite profiles were reflective of the temporal distinction between patient samples before during and after receiving therapy (1H-NMR, p < 0.001: and GC–MS p < 0.01). Disease progression and survival were strongly correlative with the GC–MS metabolite data whereas stage and cancer type were associated with 1H-NMR data. Metabolites such as hydroxylamine, tridecan-1-ol, octadecan-1-ol, were indicative of survival (GC–MS p < 0.05) and metabolites such as tagatose, hydroxylamine, glucopyranose, and threonine that were reflective of progression (GC–MS p < 0.05). Metabolite profiles have the potential to act as prognostic markers of clinical outcomes for lung cancer patients. Serial 1H-NMR measurements appear to detect metabolites diagnostic of tumor pathology, while GC–MS provided data better related to prognostic clinical outcomes, possibility due to physiochemical bias related to specific biochemical pathways. These results warrant further study in a larger cohort and with various treatment options.Electronic supplementary materialThe online version of this article (doi:10.1007/s11306-016-0961-5) contains supplementary material, which is available to authorized users.
Highlights
Lung cancer is the leading cause of cancer related deaths in both men and women in the world with 1.8 million patients in 2012 and an estimated 1.6 million deaths
We evaluated the serum metabolomic profiles of 25 lung cancer patients undergoing chemotherapy ± radiation to evaluate the feasibility of metabolites as temporal biomarkers of clinical outcomes
Serum samples from each patient collected pre-treatment, during therapy, and post-treatment were subject to both NMR and gas chromatography mass spectrometry (GC–MS) analysis
Summary
Lung cancer is the leading cause of cancer related deaths in both men and women in the world with 1.8 million patients in 2012 and an estimated 1.6 million deaths. In studies of lung cancer, most have explored the application of metabolomics for diagnosis comparing samples from lung cancer patients versus healthy volunteers (Fan et al 2009; Carrola et al 2011; Yang et al 2010) or samples from lung cancer tissues versus surrounding non-cancerous tissues (Hori et al 2011). These studies have demonstrated that many primary metabolites are found at higher levels in lung cancer tissues/patients versus controls. Wen et al (2013) utilized both GC–MS and LC– MS to reveal metabolic differences between patients with early stage adenocarcinoma of the lung and healthy controls. Lokhav et al (2013) looked at discriminating metabolomic features between patients with any stage of lung cancer versus healthy controls
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