Integration of metabolomic and transcriptomic profiles to identify biomarkers in serum of lung cancer.

We used blood serum samples collected from 31 lung cancer (LC) patients and 29 healthy volunteers in this study. Levels of serum metabolites were qualitative quantified with gas chromatography-mass spectrometry (GC-MS), and the data were analyzed by partial least-squares discrimination analysis (PLS-DA). Based on the Kyoto Encyclopedia of Genes and Genomes database, we performed pathway-based analysis utilizing metabolites presented at differential abundance between the LC serum samples and the normal healthy serum samples for systematical investigation on the metabolic alterations associated with LC pathogenesis. Finally, we analyzed the significantly enriched pathways as well as their relevant differentially expressed messenger RNAs, and drawn a correlation network plot to identify the serum metabolic biomarkers and the significantly altered metabolic pathways for LC. GC-MS analysis showed that 23 of the 169 metabolites identified were significantly different. PLS-DA model revealed that 13 of these metabolites were with variable importance>1, and particularly five were with area under curve>0.9. Pathway-based analysis demonstrated that five of eight enriched metabolic pathways were statistically significant with false discovery rate<0.05. Lastly, the correlation networks between these pathways and their related genes suggested that 29 genes had correlation degree>10, which were mainly engaged in the purine metabolism. In conclusion, we identified indole-3-lactate, erythritol, adenosine-5-phosphate, paracetamol and threitol as serum metabolic biomarkers for LC through metabolomics analysis. Besides, we identified the purine metabolism as the significantly altered metabolic pathway in LC with the help of transcriptomics analysis.