Tissue metabolic profiling of human gastric cancer assessed by 1H NMR

Abstract

BackgroundGastric cancer is the fourth most common cancer and the second most deadly cancer worldwide. Study on molecular mechanisms of carcinogenesis will play a significant role in diagnosing and treating gastric cancer. Metabolic profiling may offer the opportunity to understand the molecular mechanism of carcinogenesis and help to identify the potential biomarkers for the early diagnosis of gastric cancer.MethodsIn this study, we reported the metabolic profiling of tissue samples on a large cohort of human gastric cancer subjects (n = 125) and normal controls (n = 54) based on 1H nuclear magnetic resonance (1H NMR) together with multivariate statistical analyses (PCA, PLS-DA, OPLS-DA and ROC curve).ResultsThe OPLS-DA model showed adequate discrimination between cancer tissues and normal controls, and meanwhile, the model excellently discriminated the stage-related of tissue samples (stage I, 30; stage II, 46; stage III, 37; stage IV, 12) and normal controls. A total of 48 endogenous distinguishing metabolites (VIP > 1 and p < 0.05) were identified, 13 of which were changed with the progression of gastric cancer. These modified metabolites revealed disturbance of glycolysis, glutaminolysis, TCA, amino acids and choline metabolism, which were correlated with the occurrence and development of human gastric cancer. The receiver operating characteristic diagnostic AUC of OPLS-DA model between cancer tissues and normal controls was 0.945. And the ROC curves among different stages cancer subjects and normal controls were gradually improved, the corresponding AUC values were 0.952, 0.994, 0.998 and 0.999, demonstrating the robust diagnostic power of this metabolic profiling approach.ConclusionAs far as we know, the present study firstly identified the differential metabolites in various stages of gastric cancer tissues. And the AUC values were relatively high. So these results suggest that the metabolic profiling of gastric cancer tissues has great potential in detecting this disease and helping to understand its underlying metabolic mechanisms.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2356-4) contains supplementary material, which is available to authorized users.

Identification of Protein Phosphatase 1 Regulatory Subunit 3 as a Prognostic Biomarker in Patients with Gastric Cancer

“…The gene is a serine/threonine kinase, regulating glycogen synthesis in the liver and skeletal muscles (23)(24)(25). It has previously been shown to be actively involved in the development of Alzheimer's disease (26), hepatic steatosis 27 Actually, a decrease of choline and cholesterol in serum and tissues of patients with GC can be employed as a biomarker for early diagnosis of GC (32)(33)(34). This highlights the signi cance of defects in lipid metabolism and cell membrane biosynthesis in cancer progression.…”

Metabolic characterization of the early stage of hepatic fibrosis in rat using GC‐TOF/MS and multivariate data analyses

“…Liver fibrosis results from chronic damage to the liver in conjunction with the accumulation of extracellular matrix proteins, which is a common stage of most chronic liver diseases regardless of the etiology, and its progression may lead to hepatic cirrhosis or hepatoceluar carcinoma (Kitano & Bloomston, ; Wang et al, –c). Because the early stage of liver fibrosis can be reversed, active screening of new diagnosis and treatment methods for early interventions for HF can effectively reduce the incidence of hepatic cirrhosis, or even hepatic carcinoma, improving the quality of life for patients with HF (Feng et al, ).…”

Diagnosis of Lung Cancer: What Metabolomics Can Contribute

“…In parallel with biofluids, intact tumor tissues are frequently evaluated since intra-tumor heterogeneity is currently one of the major causes of treatment failure [33,34]. To that end, high-resolution magic angle spinning NMR (HR-MAS NMR) as an analytical approach is gaining great attention [35][36][37][38].…”