1H-NMR based metabonomic profiling of human esophageal cancer tissue

Liang Wang,Ying-Lan Zhao,Qian Bu,Huijuan Wang,Pengchi Deng,Xiaoni Shao,Tianming Wu,Youzhi Xu,Jing Hu,Longqi Chen,Jie Chen,Pu Xiang,Xiaobo Cen,Manli Li,Wenjie Lu,Hongjun Lin

doi:10.1186/1476-4598-12-25

Liang Wang, Ying-Lan Zhao + Show 14 more

Open Access

https://doi.org/10.1186/1476-4598-12-25

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Abstract

BackgroundThe biomarker identification of human esophageal cancer is critical for its early diagnosis and therapeutic approaches that will significantly improve patient survival. Specially, those that involves in progression of disease would be helpful to mechanism research.MethodsIn the present study, we investigated the distinguishing metabolites in human esophageal cancer tissues (n = 89) and normal esophageal mucosae (n = 26) using a 1H nuclear magnetic resonance (1H-NMR) based assay, which is a highly sensitive and non-destructive method for biomarker identification in biological systems. Principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA) and orthogonal partial least-squares-discriminant anlaysis (OPLS-DA) were applied to analyse 1H-NMR profiling data to identify potential biomarkers.ResultsThe constructed OPLS-DA model achieved an excellent separation of the esophageal cancer tissues and normal mucosae. Excellent separation was obtained between the different stages of esophageal cancer tissues (stage II = 28; stage III = 45 and stage IV = 16) and normal mucosae. A total of 45 metabolites were identified, and 12 of them were closely correlated with the stage of esophageal cancer. The downregulation of glucose, AMP and NAD, upregulation of formate indicated the large energy requirement due to accelerated cell proliferation in esophageal cancer. The increases in acetate, short-chain fatty acid and GABA in esophageal cancer tissue revealed the activation of fatty acids metabolism, which could satisfy the need for cellular membrane formation. Other modified metabolites were involved in choline metabolic pathway, including creatinine, creatine, DMG, DMA and TMA. These 12 metabolites, which are involved in energy, fatty acids and choline metabolism, may be associated with the progression of human esophageal cancer.ConclusionOur findings firstly identify the distinguishing metabolites in different stages of esophageal cancer tissues, indicating the attribution of metabolites disturbance to the progression of esophageal cancer. The potential biomarkers provide a promising molecular diagnostic approach for clinical diagnosis of human esophageal cancer and a new direction for the mechanism study.

Highlights

The biomarker identification of human esophageal cancer is critical for its early diagnosis and therapeutic approaches that will significantly improve patient survival
Clinical population We investigated a total of 115 samples, 89 of which were from primary esophageal cancer and 26 from normal esophageal mucosae
These results indicate that several specific metabolic pathways are disturbed in esophageal cancer tissue and, fatty acids metabolism, energy supplies and choline metabolic pathways are involved in the progression of esophageal cancer

Summary

Introduction

The biomarker identification of human esophageal cancer is critical for its early diagnosis and therapeutic approaches that will significantly improve patient survival. Those that involves in progression of disease would be helpful to mechanism research. Over the past decades the methods, such as onendoscopy-based balloon cytology and upper gastrointestinal (GI) endoscopy, have been widely used to improve the diagnosis. They have certain limitations including the poor specificity and sensitivity, resulting in detection of the disease at an advanced stage [7]. Reliable markers, especially at an early and potentially curative stage, are still unknown

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