Our proteomic analysis revealed that several enzymes of the citrate cycle and of oxidative phosphorylation were down-regulated in GC cells. These data show possible alterations in mitochondrion Cinoxacin function and a shift in energy production in the present GC cells, suggesting the Warburg effect. Proliferating tumor cells reprogram their metabolic pathways to generate energy and, thus, support the rapid cell division under stressful metabolic conditions that are characteristic of the abnormal tumor microenvironment. Even under normal oxygen concentrations, tumor cells shift from ATP generation through oxidative phosphorylation to ATP generation through glycolysis, converting most incoming glucose to lactate. It has been proposed that highly active glycolysis provides a biosynthetic advantage for tumor cells. Glycolysis provides enough metabolic intermediates by avoiding the oxidation of glucose, which is essential for the synthesis of macromolecules, such as lipids, proteins, and nucleic acids, during cell division. The lactate dehydrogenase and pyruvate dehydrogenase complexes control the metabolism of pyruvic acids, transforming to either lactic acids or acetyl-CoA 
then entering the citrate cycle. The down-regulation of subunits of the LDH and PDH complexes suggests a reduction in pyruvate flux into the citrate cycle and a decrease in the rate of oxidative phosphorylation and oxygen consumption, reinforcing the glycolytic phenotype. Other down-regulated proteins, such as LIPF and GOT1, highlight the activation of other metabolic pathways with the impairment of the citrate cycle and oxidative phosphorylation. Several metabolic alterations that we observed in noncardia GC were also described by Cai et al. in a cardia GC proteomic study, suggesting that these metabolic alterations are not specific to a GC subtype based on tumor location. By the PANTHER system, the most significantly enriched pathway is the p53 pathway observed in the comparison between tumor and control samples. Additionally to its function in the DNA damage response and apoptosis, p53 is also a regulator of cell metabolism. p53 promotes oxidative phosphorylation and also inhibits the glycolytic pathway by up-regulating the expression of TP53-induced glycolysis and the apoptosis regulator. Therefore, the loss of p53 contributes to the acquisition of glycolytic phenotype. The loss of TP53 locus is a common finding in GC of individuals from Northern Brazil. Moreover, 20% of the GC analyzed by 2-DE presented p53 immunoreactivity. The p53 immunoreactivity usually depends on accumulation of mutated proteins in the cell, which leads to a longer half-life. The top networks of molecular interactions and functions were also identified using the IPA software. We showed several differently regulated proteins involved in cellular assembly and organization, and in inflammatory processes. The cellular assembly and organization was the principally enriched network observed in the comparison between controls and tumors with lymph node metastasis. Therefore, our data reveal that the molecules of the described subnetwork are important to the process of metastasis in noncardia Lomitapide Mesylate gastric carcinogenesis. Previous studies have demonstrated that GC is strongly linked to chronic inflammation, and that infection with H. pylori may trigger the chronic inflammation that can lead to malignancy. However, the exact mechanism of this process is still not known. The identified proteins add new pieces to this process in gastric carcinogenesis. The unsupervised hierarchical clustering of the differentially expressed proteins revealed that the tumors and control samples do not form two distinct separate clusters. Although, hierarchical clustering revealed one group composed by only controls, the other group presented all tumor samples and two misclassified control samples.