Potential role of metabolomics in diagnosis and surveillance of gastric cancer

Abstract

Gastric cancer is one of the deadliest cancers worldwide, and is especially prevalent in Asian countries. With such high morbidity and mortality, early diagnosis is essential to achieving curative intent treatment and long term survival. Metabolomics is a new field of study that analyzes metabolites from biofluids and tissue samples. While metabolomics is still in its infancy, there are numerous potential applications in oncology, specifically early diagnosis. Only a few studies in the literature have examined metabolomics’ role in gastric cancer. Various fatty acid, carbohydrate, nucleic acid, and amino acid metabolites have been identified that distinguish gastric cancer from normal tissue and benign gastric disease. However, findings from these few studies are at times conflicting. Most studies demonstrate some relationship of cancer cells to the Warburg Effect, in that glycolysis predominates with conversion of pyruvate to lactate. This is one of the most consistent findings across the literature. There is less consistency in metabolomic signature with respect to nucleic acids, lipids and amino acids. In spite of this, metabolomics holds some promise for cancer surveillance but further studies are necessary to achieve consistency and validation before it can be widely employed as a clinical tool.

Keywords: Gastric cancer; Metabolomics; Screening; Biomarkers; Surveillance

Core tip: There are differences in metabolomic profiles of gastric cancer patients and healthy controls, as well as between different stages of gastric cancer. The transition from normal to malignant consistently shows upregulation in lactate and downregulation of glucose consistent with the Warburg effect. This trend is perpetuated as cells advance from non-invasive to invasive. Key tricarboxylic acid (TCA) cycle intermediates and amino acids are elevated as a result of anaplerotic reactions. Perpetuation of the TCA cycle generates energy for essential cell functions. There is less consistency between lipid and nucleic acid metabolites.