Exploratory investigation of plasma metabolomics in human lung adenocarcinoma

Abstract

Globally lung cancer is common among males and recently also noted with increasing incidences in females, especially adenocarcinoma. Further, most lung cancers are not easily detected until the late stage. Metabolic profiling of plasma low molecular weight metabolites may help unveil the complex pathophysiological changes during early lung adenocarcinoma development. Here we used a combination of gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) methods to investigate the metabolic signatures in the plasma of 31 stage I human lung adenocarcinoma patients and 28 healthy controls. The metabolic profiles were assayed using orthogonal projections to latent structures discriminant analysis (OPLS-DA), and were further analyzed to identify the associated marker metabolites. The OPLS-DA models derived from both GC-MS and LC-MS showed significant discriminations in metabolic profiles between cases and healthy controls. It was found that around 37 metabolites contributed to the differences. The alterations of these metabolites implied disturbances in amino acids, lipids, fatty acids and glutaminolysis metabolism in human lung adenocarcinoma, even after removal of influencing factors such as age, gender and smoking habits. Of particular interest, the sex hormone metabolic pathway involving the sulfate conjugate of testosterone, androsterone and pregnenolone was found to be disturbed considerably. All these metabolic perturbations occur at an early stage of lung adenocarcinoma and thus could act as biomarkers for its early diagnosis. These exploratory findings suggest that integration of two sensitive and complementary metabolomic approaches enables a comprehensive metabolite profiling for human lung adenocarcinoma, although a more extensive study is needed to confirm the findings.