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

Abstract

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 pathwaybased 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. K E Y W O R D S lung cancer, metabolomics, serum, transcriptomics | INTRODUCTIONTo date, lung cancer (LC) has become one of the most common cancer all over the world, with 1.8 million new cases of LC and 1.6 million deaths in 2012. 1 In spite of great efforts in early diagnosis of LC, it still remained the leading cause of cancer-related deaths in men and the second leading cause in women second to breast cancer. 1 Currently, common diagnostic approaches included chest radiograph, computed tomography scan, fiberoptic bronchoscopy, magnetic resonance imaging and positron emission tomography. 2 Unfortunately, these techniques hardly provide useful

Chronic Heat Stress Induces Acute Phase Responses and Serum Metabolome Changes in Finishing Pigs

“…Metabolites are considered as both the building blocks of animal development and the regulators of animal health [27]. Metabolites in blood are reported to be highly responsive to environmental stress [28]. In the present study, twenty four metabolites whose concentrations were significantly affected by chronic HS were identified using the GC-MS-based metabonomic approach.…”

Genome-Wide Transcriptome and Metabolome Analyses Provide Novel Insights and Suggest a Sex-Specific Response to Heat Stress in Pigs

“…Metabolites are building blocks for growth and development; they are also key regulators and markers of animal health [87]. Blood metabolites are highly sensitive to environmental stress [88] and HS alters protein metabolism in a number of species [19,[89][90][91]. Metabolome analysis showed that several plasma metabolites were enriched in response to HS in both male and female groups, this included, creatinine, histidine, lysine, methionine, ornithine, serine, proline and pyruvate, while 4-aminobutryic acid, Creatine, Taurine and Urea concentration was lower post HS.…”

Зміни Метаболізму Пуринів При Кістково-Суглобовій Формі Раку Легені

“…Было установлено, что гиперурикемия является фактором риска развития и последующего тяжелого течения РЛ [9,10]. Считается, что пуриновые основания относятся к биомаркерам костных метастазов при РЛ, но их диагностическая и прогностическая значимость пока еще не определена [11].…”