Screening for Early Gastric Cancer Using a Noninvasive Urine Metabolomics Approach.

Abstract

Simple SummaryThere are currently no effective specific biomarkers for the screening of early gastric cancer. Recently, metabolomics has been used to profile small endogenous metabolites, demonstrating significant potential in the diagnosis/screening of cancer, owing to its ability to conduct a noninvasive sample analysis. Here, we performed a urine metabolomics analysis in the context of an early diagnosis of gastric cancer. This approach showed very high diagnostic sensitivity and specificity and performed significantly better than the analysis of serum tumor markers modalities. An additional genomic data analysis revealed the up-regulation of several genes in gastric cancer. This metabolomics-based early diagnosis approach may have the potential for mass screening an average-risk population and may facilitate endoscopic examination through risk stratification.The early detection of gastric cancer (GC) could decrease its incidence and mortality. However, there are currently no accurate noninvasive markers for GC screening. Therefore, we developed a noninvasive diagnostic approach, employing urine nuclear magnetic resonance (NMR) metabolomics, to discover putative metabolic markers associated with GC. Changes in urine metabolite levels during oncogenesis were evaluated using samples from 103 patients with GC and 100 age- and sex-matched healthy controls. Approximately 70% of the patients with GC (n = 69) had stage I GC, with the majority (n = 56) having intramucosal cancer. A multivariate statistical analysis of the urine NMR data well discriminated between the patient and control groups and revealed nine metabolites, including alanine, citrate, creatine, creatinine, glycerol, hippurate, phenylalanine, taurine, and 3-hydroxybutyrate, that contributed to the difference. A diagnostic performance test with a separate validation set exhibited a sensitivity and specificity of more than 90%, even with the intramucosal cancer samples only. In conclusion, the NMR-based urine metabolomics approach may have potential as a convenient screening method for the early detection of GC and may facilitate consequent endoscopic examination through risk stratification.